StudyFinder
Search Results Within Category "Blood Disorders"
39 Study Matches
A Study of Emapalumab for Pediatric Aplastic Anemia
Anthony Sabulski, MD - anthony.sabulski@cchmc.org
ALL
0 years to 25 years old
PHASE2
NCT06430788
Inclusion Criteria:
* Patients undergoing workup for suspected newly diagnosed sAA:
* Patients with severe cytopenias and a hypocellular marrow concerning for sAA
* Patients that meet the definition for suspected sAA (Camitta Criteria) as follows:
Marrow Cellularity: \<25%, or 25-50% with \<30% residual hematopoietic cells Peripheral cytopenias (at least 2 of 3) Absolute neutrophil count (ANC): \<500 x 10\^9/L Platelets: \<20 x 10\^9/L Absolute Reticulocyte Count: \<60 x 10\^9/L
* Patients that do not have evidence of leukemia or MDS
* Patients \< 25 years of age at time of diagnosis
* Able to tolerate emapalumab and IST (with standard institutional organ function criteria)
Exclusion Criteria:
* Uncontrolled infection at presentation.
* Patients who have undergone previous treatment for sAA.
* Patients with known inherited bone marrow failure
* Patient who has completed a full workup for sAA including having results back from telomere testing, DEB and genetics (when applicable), as well as having an appropriate willing and available donor and would otherwise be admitted for HSCT within 2 weeks of enrolling on the trial
* Patients with leukemia or MDS
* Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests. BIOLOGICAL: Emapalumab
Aplastic Anemia, Cytopenia, Hypocellular Marrow
pediatric aplastic anemia, aplastic anemia, cytopenia, hypocellular marrow, Emapalumab, Memorial Sloan Kettering Cancer Center, 23-278
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
- cancer@cchmc.org
ALL
0 years to 38 years old
NCT06131801
Inclusion Criteria:
* Age: Patients must be \<39 years of age at time of study enrollment
* Diagnosis: Patients may have a diagnosis of any hematologic malignancy
* Central access: Patients must have an existing venous or arterial access line for PK blood draws
* Weight requirement: Patients must weigh at least 5.5 kg at the time of enrollment
* Venetoclax: Patients must be receiving any dose of venetoclax given as a solution made from crushed tablets by mouth (PO) or via nasogastric (NG), or G-tube as prescribed by their treating oncologist.
* Concurrent chemotherapy medications: Patients may receive venetoclax as a single agent or in combination with any other chemotherapeutic agents.
Exclusion Criteria:
* Pregnant women are excluded from this study because venetoclax has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax.
* Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion. OTHER: 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.
Hematologic Malignancy, Leukemia, Lymphoma, Acute Lymphocytic Leukemia, ALL, Acute Myelogenous Leukemia, AML, Chronic Myelogenous Leukemia, CML, Myeloproliferative Neoplasm, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Burkitt Lymphoma, T-cell Lymphoma, B Cell Lymphoma, Peripheral T Cell Lymphoma, Cutaneous B-Cell Lymphoma
Venetoclax, Pediatric AML, Pediatric Relapsed/Refractory AML
Mirdametinib in Histiocytic Disorders
Monica Trapp - Monica.Trapp@cchmc.org
ALL
2 years and over
PHASE2
NCT06153173
Inclusion Criteria:
• Subjects must be ≥ 2 years of age AND have a diagnosis of a histiocytic disorder that requires systemic therapy * If patient has had a diagnostic biopsy, biopsy must be reviewed and confirmed by CCHMC pathologist as feasible * If patient has had a biopsy but has not had molecular testing done, must have tissue available for mutational analysis * If patient has isolated pituitary/CNS disease or situations where biopsy is not feasible, positive ddPCR blood test for mutation associated with histiocytic neoplasm with clinical features of histiocytosis is sufficient
• Must have measurable disease on PET scan or brain MRI
• Subjects must demonstrate adequate organ function as defined: * Renal: maximum serum creatinine 2x the upper limit of normal (ULN) OR a creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 * Liver: ALT ≤ 3x ULN AND normal INR (≤ 1.5) * Hematologic: Hematology: Albumin ≥ 2.8 g/dL; Absolute neutrophil count ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L; Hemoglobin ≥ 9.0 g/dL * Patients with organ function abnormalities outside of these thresholds deemed to be the result of histiocytic disease will be considered eligible
Exclusion Criteria:
• Prior therapy with stipulations as described: * Myelosuppressive Chemotherapy: Must not have received any cytotoxic chemotherapy which impacts the growth and development of cells in the bone marrow within 14 days of enrollment onto this study (i.e. cytarabine, cladribine, clofarabine, mercaptopurine, methotrexate, vinblastine) * MEK Inhibitors: Must not have received a MEK inhibitor within 30 days (or 5 half-lives, whichever is longer) of enrollment, NOR have had disease progression on MEK inhibitor * Steroids: Due to the increased risk of an ocular event, the use of systemic oral, inhaled, or ocular glucocorticoid therapy is prohibited within 14 days prior to first dose of mirdametinib. Throughout the treatment period, short term glucocorticoid treatment (30 days or less) is permitted. Any patients requiring long-term steroid use (more than 30 consecutive days) are not eligible. The exception to this rule is subjects with endocrine deficiencies who require physiologic steroids * Radiation: Must not have received radiation within 14 days of study enrollment or have received radiation to the orbit at any time
• Risk factors for retinal vein occlusion (RVO) are listed. Exclusion should be considered by clinical discretion if they have any of the following risk factors for RVO at screening: * Intraocular pressure (IOP) \> 21 mmHg; if IOP is unable to be obtained (eg age, cooperation, tolerability), ophthalmologist's exam findings and overall assessment will be utilized. If in the ophthalmologist's assessment there are no signs of raised IOP, the subject will be considered eligible for this parameter * Glaucoma or any significant abnormality (≥ grade 2) on ophthalmologic exam that is uncontrolled with intervention * Serum cholesterol \> 300 mg/dL * Serum triglycerides \> 300 mg/dL * Hyperglycemia (either fasting blood glucose \> 125 mg/dL OR random blood glucose \> 200 mg/dL) * Uncontrolled hypertension (participants ≤ 12 years of age with a blood pressure ≥ 95th percentile for age + 12 mmHg; participants ≥ 13 years of age with a blood pressure ≥ 140/90 mm Hg) unresolved on repeat measurement
• LVEF \< 55% at screening OR history of clinically significant cardiac disease, unless deemed to be the direct result of disease
• Subjects who are pregnant or breastfeeding, or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study
DRUG: Mirdametinib
Langerhans Cell Histiocytosis (LCH), Juvenile Xanthogranuloma (JXG), Rosai-Dorfman Disease (RDD), Histiocytic Disorders
HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy (RAFA)
Jamie Wilhelm - jamie.wilhelm@cchmc.org
ALL
3 month(s) and over
PHASE2
NCT02143830
Inclusion Criteria:
* Patients must have a diagnosis of Fanconi anemia
* Patients must have one of the following hematologic diagnoses:
• Severe Aplastic Anemia (SAA), with bone marrow cellularity of \<25% OR Severe Isolated Single Lineage Cytopenia and at least one of the following features:
• Platelet count \<20 x 109/L or platelet transfusion dependence\*
• ANC \<1000 x 109/L
• Hgb \<8 gm/dl or red cell transfusion dependence\*
• Myelodysplastic Syndrome (MDS) (based on WHO or IPSS Classification
• Acute Myelogenous Leukemia (untreated, in remission or with refractory or relapsed disease) * Donors will be either human leukocyte antigen (HLA) compatible unrelated or HLA-genotypically matched related donors (no fully matched sibling donor). * Patients and donors may be of either gender or any ethnic background. * Patients must have a Karnofsky adult, or Lansky pediatric performance scale status \> 70%. * Patients must have adequate physical function measured by:
• Cardiac: asymptomatic or if symptomatic then 1) left ventricular ejection fraction (LVEF) at rest must be \> 50% and must improve with exercise or 2) Shortening Fraction \> 29%
• Hepatic: \< 5 x upper limit of normal (ULN) alanine transaminase (ALT) and \< 2.0 mg/dl total serum bilirubin.
• Renal: serum creatinine \<1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 50 ml/min/1.73 m2
• Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted * Each patient must be willing to participate as a research subject and must sign an informed consent form. * Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study.
Exclusion Criteria:
* Active CNS leukemia
* Female patients who are pregnant (positive serum or urine HCG) or breast-feeding.
* Active uncontrolled viral, bacterial or fungal infection
* Patient seropositive for HIV-I/II; HTLV -I/II DRUG: Busulfan, DRUG: Cyclophosphamide, DRUG: Fludarabine, DRUG: rabbit ATG, DRUG: G-CSF, BIOLOGICAL: Peripheral blood stem cell
Fanconi Anemia, Severe Marrow Failure, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia (AML)
marrow aplasia, cytopenia, myelodysplasia, AML, bone marrow transplant, cytoreductive regimen, T-cell reduction
Prevention of Bleeding in Patients With Moderate and Severe Hemophilia A Playing Sports: A Comparison Between Factor VIII and Emicizumab Prophylaxis (STEP)
Abigail Abigail Torres - abigail.torres@cchmc.org
ALL
6 years to 19 years old
NCT05022459
Inclusion Criteria:
• Participant (if 18 years of age or older) or parent/LAR is willing and able to provide written informed consent; minor participant is willing and able to provide assent, if applicable based on site and local regulations
• Males and females between 6 to ≤ 19 years of age at time of enrollment with moderate to severe Hemophilia A (FVIII activity ≤ 5%) without inhibitors are eligible for participation in this study
• Participants must be on Emicizumab or standard FVIII prophylaxis per institutional/primary hematologist recommendations
• Participants must be engaging in or registered to start participating in one or more sports activities with moderate to high risk of bleeding as defined by the NHF- Playing it Safe guidelines (numerical rating \>/= 2).
• Participant must be willing to keep activity, bleed, and treatment logs for the duration of the study
Exclusion Criteria:
• Participant/parent/LAR unwilling to provide informed consent/assent
• Unwilling to log or document bleeds and treatment information as per study guidelines
• Participants with any other bleeding disorders will be excluded
• Patients who are pregnant, planning to become pregnant, or breastfeeding should not be enrolled in the study
• Participants on concomittent FVIII replacement and emicizumab for sports participation
DRUG: Emicizumab, DRUG: FVIII
Hemophilia A
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
- cancer@cchmc.org
ALL
Up to 22 years old
PHASE1
NCT04726241
Inclusion Criteria:
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must have one of the following at the time of study enrollment:
* Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol
* This includes isolated myeloid sarcoma
* Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
* Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:
* Second or greater B-ALL medullary relapse, excluding KMT2Ar
* Any first or greater B-ALL medullary relapse involving KMT2Ar
* Any first or greater T-ALL medullary relapse with or without KMT2Ar
* Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome
Integrative Training Program for Pediatric Sickle Cell Pain (I-STRONG SCD)
Katie Katie Beasley - Katie.Beasley@cchmc.org
ALL
12 years to 18 years old
NA
NCT06691867
Inclusion Criteria:
* Provision of signed and dated informed consent form for adolescents 18 years old and caregivers' participation
* For children \<18, informed assent and parental informed consent to participate in the study
* Willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study
* Males and females; Ages 12-18 years for adolescents; no age limitations for caregivers
* Documented diagnosis of sickle cell disease (any genotype) for adolescents
* Adolescent scores at least 3 on the Pediatric Pain Screening Tool
* Adolescent reports typical pain intensity in the past week at least 4 on a 0-10 cm Visual Analog Scale
* Adolescent on stable disease-modifying treatments, if applicable (e.g., hydroxyurea, glutamine, voxelotor, crizanlizumab) as defined by not newly initiated or significantly increased dosages (mg/kg) in the past 3 months
* Speak and read English
Exclusion Criteria:
* An adolescent has comorbid medical conditions typically associated with pain but unrelated to SCD (e.g., rheumatologic disorders or inflammatory bowel disease)
* Adolescent has undergone genetic or hematopoietic stem cell therapy
* Presence of a condition(s) or diagnosis, either physical or psychological, or physical exam finding that precludes participation
* Adolescents receiving active treatment (e.g., weekly appointments with a provider) for nonpharmacological therapies (e.g., structured behavioral pain management, physical therapy, or acupuncture program) that overlap with the active phase of the study intervention BEHAVIORAL: I-STRONG, OTHER: Enhanced Usual Care (EUC)
Sickle Cell Disease
Sickle Cell Pain, Lifestyle considerations, Pediatrics, Behavioral intervention, Mind-body intervention
CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
cancer@cchmc.org
ALL
18 years and over
PHASE1
NCT05143996
Inclusion Criteria:
• Aged ≥ 18 years of age.
• Willing and able to give written informed consent and adhere to protocol requirements; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations, and serial samples of bone marrow and peripheral blood.
• Patient has a confirmed diagnosis of recurrent or refractory AML or MDS.
• Patient has received, and has progressed, recurred, or is intolerant of approved therapeutic options that are available, or declines treatment with these therapies.
• White blood cell (WBC) count at the time of the first dose is \< 20,000/uL (hydroxyurea is permitted according to standard institutional practice). Following first dose, WBC should be checked prior to subsequent CLN-049 administration and if WBC \> 20,000/μL, CLN-049 treatment should be postponed (see Section 6.1 for further guidance).
• Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2.
• Toxicities related to prior study therapy should have resolved to Grade 1 or less according to criteria of NCI CTCAE v5.0, except for alopecia, lymphopenia, neutropenia, leukopenia, anemia, thrombocytopenia. Patients with chronic but stable toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
• The patient's laboratory values meet the following criteria:
• Creatinine clearance (CrCl) as calculated by the Cockcroft-Gault formula (Appendix 1) must be ≥ 60 mL/min;
• Total bilirubin ≤ 1.5 × ULN. This does not apply for patients with confirmed Gilbert's Syndrome, hemolysis, or chronic blood transfusions, for whom total bilirubin must be less than 3.0 mg/dL with a conjugated bilirubin less than 0.5 mg/dL;
• AST and ALT ≤ 3.0 × ULN (unless attributed to leukemic involvement).
Exclusion Criteria:
• Diagnosis of acute promyelocytic leukemia (APL)
• Active central nervous system (CNS) leukemia. For patients with a history of CNS leukemia, a lumbar puncture should be performed during screening to exclude the presence of active CNS involvement.
• Isolated extramedullary relapse
• Prior organ allograft
• Allogeneic hematopoietic transplantation within six months of treatment, or with clinical or laboratory evidence of GVHD, or requiring ongoing treatment with immune suppression within 2 months of the first dose of CLN-049.
• Treatment with any of the following:
• Radiation therapy (XRT) within 28 days of the first dose of CLN049, or craniospinal XRT within 8 weeks of the first dose of CLN-049, or history of total body irradiation (TBI).
• Prior immunotherapy with checkpoint inhibitors ≤ 42 days prior to the first dose of CLN-049.
• Prior history of chimeric antigen receptor (CAR-T) cell therapy or other modified T cell therapy.
• Anti-leukemic therapy except hydroxyurea for cytoreduction, and intrathecal chemotherapy ≤ 14 days or 5 half-lives, whichever is shorter, prior to the first dose of CLN-049.
• Short-acting hematopoietic growth factors ≤ 7 days prior to the first dose of CLN-049
• Long-acting growth factors ≤ 14 days prior to the first dose of CLN-049.
• Systemic glucocorticoid therapy (except equivalent of \< 10 mg prednisone daily) or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049 (see separate guidelines for patients who are post allogeneic hematopoietic transplantation). The transient use of corticosteroids for transfusion premedication or the treatment of infusion or transfusion reactions will not be considered for this criterion. Topical corticosteroids and steroid eye drops are allowed, and will not exclude the patient from eligibility.
• Prior treatment with a FLT3-directed bispecific molecule, or a FLT3-targeted antibody.
• Currently participating/previously participated in an interventional study and received an investigational drug within 14 days (or five half-lives, whichever is longer) prior to the first dose of CLN-049.
• Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
• Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications, except for patients with vitiligo, psoriasis (in consultation with the Sponsor), resolved childhood asthma/atopy or autoimmune thyroid disorders on stable thyroid hormone supplementation.
• A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
• Any concurrent condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
• Active uncontrolled infection within seven days of first dose of CLN-049. Prophylactic use of systemic antiviral, antibacterial, or antifungal agents for treatment of chronic, controlled infection or as prophylaxis is permitted.
• Has a history of, or a positive test for Human Immunodeficiency Virus (HIV) 1/2 or primary immunodeficiency disease such as HIV.
• Known history of hepatitis B (with positive testing for either hepatitis B surface antigen \[HBsAg\] or hepatitis B core Ab), hepatitis C (HCV) infection (with positive testing for HCV antibody and/or HCV ribonucleic acid \[RNA\] in serum), or acute hepatitis A (with positive testing for hepatitis A IgM). Note: patients with chronic HCV with undetectable viral load defined by sustained virologic response 24 weeks (SVR24) after completion of anti-hepatitis C treatment will be eligible. Patients with hepatitis B surface antigen \[HBsAg\] or hepatitis B core Ab with negative viral load will be eligible.
• Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection including history of positive SARS-CoV-2 testing without subsequent documentation of negative test results, patients with results that are pending but not yet known, or patients with suspected active infection based on clinical features
• History of the following events in conjunction with prior treatment with immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law.
• Live virus vaccines within 28 days of the first dose of CLN-049, during treatment, and until the end of last dose of CLN-049.
• Woman of child-bearing potential (WOCBP) who is pregnant or breast-feeding, plans to become pregnant within 120 days of last study drug administration, or declines to use an acceptable method to prevent pregnancy during study treatment and for 120 days after the last dose of study drug administration.
• Male patient who plans to father a child or donate sperm within 120 days of last study drug administration, or who has a partner who is a WOCBP, and declines to use acceptable method to prevent pregnancy during study treatment and for 120 days after the last dose of study drug administration.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds.
• Patient has history of drug-related anaphylactic reactions to any components of CLN-049. History of Grade 4 anaphylactic reaction to any bispecific molecule or monoclonal antibody therapy.
• Known history of prior human anti-human antibody response. Patients will not be screened for human anti-human antibody prior to study participation.
• Known active alcohol or drug abuse.
• Patients who are incapacitated or involuntarily incarcerated.
DRUG: CLN-049
Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
Kenzie Nolte - mackenzie.nolte@cchmc.org
ALL
NCT04398628
Participants who meet the following inclusion criteria and none of the exclusion criteria are eligible for enrollment in one of the open disease-specific arms.
• Any age
• Having a congenital or acquired blood disorder; or
• Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
• Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.
• Eligible for a currently active disease-specific arm.
• Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.
• Factor VIII or factor IX activity \<50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR
• Carrier for congenital hemophilia with a factor VIII \>=50% or factor IX activity \>=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR
• Known congenital hemophilia that have a factor level \>50% after receiving vector, OR 4. Acquired hemophilia.
• Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
• Abnormalities of platelet granules
• Abnormalities of platelet signal transduction
• Abnormalities of platelet secretion
• Collagen Receptor Defect
• ADP Receptor Defect
• Thromboxane Receptor Defect
• Giant Platelet Disorder
• Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)
• PAI-1 deficiency
• Factor I, II, V, VII, X, XI, XIII deficiencies
• Combined FV and FVIII deficiency
• Plasminogen deficiency
• Decreased tissue plasminogen activator
• Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia
• Thrombotic Thrombocytopenia Purpura or Congenital Hemolytic Uremic Syndrome
• Wiskott-Aldrich
• Methylenetetrahydrofolate Reductase Deficiency
• Have a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years with an unknown diagnosis, OR
• Connective tissue disorder with bleeding tendency as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years.
• Diagnosis of congenital hemophilia A (FVIII \<40%) or hemophilia B (FIX \<40% or below lower limit for age)
• Age \<18 years at time of enrollment
• Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent
• Care established at one of the ATHN Transcends participating HTCs
• Clotting Factor Concentrate (CFC) exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets \<3 exposure days (ED) Exclusion Criteria
• Concomitant diagnosis with another bleeding disorder
• History of a confirmed, positive inhibitor INHIBIT Module
• Concomitant diagnosis with bleeding disorder other than hemophilia A
• Immune disorder
• Previous history or presence of factor VIII inhibitor. A confirmed, positive inhibitor is defined as two consecutive positive inhibitor titers (≥ 0.6 BU) that result in changes in treatment recommendations. Efanesoctocog alfa (ALTUVIIIO®) Module Inclusion criteria:
• Ability of the potential participant's legally authorized representative (e.g., their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulation.
• People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists \<5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of \<1%.) Other severities may be included per ATHN Transcends PI approval.
• \<18 years of age.
• No history of a confirmed, positive FVIII inhibitor.
• Sex assigned at birth of male, female, or intersex.
• Participants should have no more than three (3) exposure days of blood products (fresh frozen plasma, cryoprecipitate, or platelets), no more than three (3) doses of any FVIII concentrate other than efanesoctocog alfa, and up to three (3) doses of efanesoctocog alfa prior to enrollment.
• Site PI confirmed all inclusion criteria has been met. Exclusion criteria:
• Not meeting all the inclusion criteria; confirmed by site PI.
• Any exposure to blood products or FVIII replacement products except as described in the inclusion criteria.
• History of positive inhibitor testing.
• History of hypersensitivity reactions associated with efanesoctocog alfa administration.
• Other coagulation disorder(s) in addition to Hemophilia A.
• Any concurrent clinically significant major disease such as cancer that, in the opinion of the investigator, would make the participant unsuitable for enrollment.
• Concurrent systemic treatment with chemotherapy and/or other immunosuppressant medications. Use of corticosteroids for the treatment of asthma or management of acute allergic or otherwise life-threatening episodes is allowed except for systemic corticosteroid treatment given to children daily or on an alternate day schedule at \> 2 mg/kg/day of prednisone or its equivalent or \> 20 mg/day if the duration is longer than 14 days.
• Enrollment in a concurrent clinical interventional drug study.
• Intake of an Investigational Medicinal Product within three (3) months prior to inclusion in this study.
• Inability to comply with study requirements.
• Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment. Hemophilia Natural History Arm Inclusion Criteria
• Congenital or acquired hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility, OR
• Females of any age, with confirmed congenital hemophilia A or B carrier status with genetic mutational analysis and any factor level. Exclusion Criteria
• Presence of any known bleeding disorder other than congenital hemophilia A or B
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded)
• Unable or unwilling to comply with the study arm protocol. Nonacog beta pegol (Rebinyn®) Module
• Has provided signed written consent for the nonacog beta pegol (Rebinyn®)Module before any study-related activities.
• Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment. Additional doses may be allowable per ATHN Transcends PI approval.
• Decision to initiate continuous prophylaxis treatment with commercially available nonacog beta pegol has been made by the participant(s)/Legally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.
• Previous participation in this study. Participation is defined as having given informed consent in this study.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.
• Known or suspected hypersensitivity to nonacog beta pegol or related products.
• Clinical suspicion or presence of FIX inhibitor at time of inclusion.
• Inability or unwillingness to undergo neurological assessment/structured developmental history. Emicizumab (Hemlibra®) Module
• Participant currently treated with emicizumab (Hemlibra®)
• Currently enrolled in the Hemophilia Natural History Arm of ATHN Transcends
• Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility
• Age 18 years of age or older
• English speaking
• Presence of any known bleeding disorder other than congenital hemophilia A or B;
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded); and
• Unable or unwilling to comply with the study arm protocol Hemophilia Gene Therapy Outcomes Arm Inclusion Criteria
• Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.
• Age 18 years and older.
• Able to give informed consent. Exclusion Criteria None Etranacogene dezaparvovec (HEMGENIX®) Module
• Age 18 years of age or older
• Treatment with commercial etranacogene dezaparvovec (HEMGENIX®)
• Have provided signed written informed consent within 3 months before or within 6 months after etranacogene dezaparvovec (HEMGENIX®) treatment, or within 6 months of when the study is initiated at the treating site. FIX Prophylaxis Cohort
• Age 18 years of age or older
• Treatment with FIX prophylaxis therapy
• Has provided signed written consent at any time for ATHN Transcends Study Exclusion Criteria, both cohorts: 1\. Have been treated with etranacogene dezaparvovec in a clinical trial prior to commercial availability. These patients are still eligible for enrollment in the Gene Therapy Outcomes Arm, and their data may be collected for separate analysis. Congenital Platelet Disorders Arm Inclusion Criteria
• Platelet adhesion defect
• Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to vWF)
• Velocardio-facial syndrome/DiGeorge syndrome (Defective GPIb-IX-V receptor)
• Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between vWF-GP1bα)
• Platelet aggregation defect
• Glanzmann thrombasthenia (Defective integrin αIIbβ3 (GPIIb/IIIa)
• Platelet aggregation defect, NOS
• Agonist receptor defects
• Epinephrine
• ADP
• Collagen
• Thromboxane A2
• Platelet signaling defects
• Cyclooxygenase deficiency (PTGS1 mutation)
• Phospholipase A2 deficiency
• Thromboxane synthase deficiency (TBXAS1 mutation)
• G protein activation defect (GNAS mutation)
• Scott syndrome (defect in phosphatidyl serine translocation)
• Platelet Granule disorders
• Dense granule storage pool disorder * Hermansky Pudlak syndrome * Chediak Higashi syndrome * Griscelli syndrome
• Alpha granule storage pool disorder * Grey platelet syndrome * Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome * Quebec platelet disorder * Paris-Trousseau syndrome
• Combined alpha delta granule deficiency
• Platelet cytoskeletal structure defects
• Wiskott Aldrich syndrome
• MYH9 associated disorders (myosin heavy chain) * May Hegglin syndrome * Fechtner syndrome * Sebastian syndrome * Epstein syndrome
• Other mutations * FLNA mutations (Filamin) * DIAPH1 (Actin and microtubules) * ACTN1 (alpha actinin) * TPM4 (tropomyosin) * TUBB1 (beta tubulin)
• Other Congenital thrombocytopenias
• Familial platelet disorders and predisposition to AML (RUNX1)
• X linked thrombocytopenia with dyserythropoiesis (GATA1)
• Congenital amegakaryocytic thrombocytopenia (MPL) Exclusion Criteria
• Diagnosis of von Willebrand Disease (Meeting the definition of vWD or low vWF per most recent international guidelines)
• Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX ≤ 40%) Glanzmann Thrombasthenia (GT) Module Inclusion Criteria
• Participant has signed the informed consent/assent form
• Participant has flow cytometry or aggregometry or genetics confirmed GT
• Participant is willing to perform study procedures, including daily bleed tracking for 3 months and further if requested
• Participants are 2 years or older at time of consent Exclusion Criteria None
Inclusion Criteria:
• Any age
• Having a congenital or acquired blood disorder; or
• Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
• Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.
• Eligible for a currently active disease-specific arm.
• Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.
Exclusion Criteria:
1\. Does not qualify for inclusion in a currently activedisease-specific arm; participants may be eligible to enroll as future cohorts and arms are activated; 2. Unable to give informed consent or assent 3. Unwilling to perform study procedures
Cohort Participant Selection
Each participant is to be enrolled in the cohort for which they qualify as defined below.
Hemophilia Cohort
Inclusion Criteria:
Participants who meet any of the following inclusion criteria are eligible for enrollment into this cohort:
• Factor VIII or factor IX activity \<50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR
• Carrier for congenital hemophilia with a factor VIII \>=50% or factor IX activity \>=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR
• Known congenital hemophilia that have a factor level \>50% after receiving vector, OR 4. Acquired hemophilia.
Exclusion Criteria:
None
Von Willebrand Disease Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Meeting the definition of VWD or low VWF per most recent international guidelines
Exclusion Criteria:
None
Congenital Platelet Disorders Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
• Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
• Abnormalities of platelet granules
• Abnormalities of platelet signal transduction
• Abnormalities of platelet secretion
• Collagen Receptor Defect
• ADP Receptor Defect
• Thromboxane Receptor Defect
• Giant Platelet Disorder
• Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)
Exclusion Criteria:
1\. Platelet disorders secondary to medications or other substances
Rare Disorders Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the following:
• PAI-1 deficiency
• Factor I, II, V, VII, X, XI, XIII deficiencies
• Combined FV and FVIII deficiency
• Plasminogen deficiency
• Decreased tissue plasminogen activator
• Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia
• Thrombotic Thrombocytopenia Purpura or Congenital Hemolytic Uremic Syndrome
• Wiskott-Aldrich
• Methylenetetrahydrofolate Reductase Deficiency
Exclusion Criteria:
None
Bleeding NOS Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
• Have a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years with an unknown diagnosis, OR
• Connective tissue disorder with bleeding tendency as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years.
Exclusion Criteria:
None
Thrombosis/Thrombophilia Cohort
Inclusion Criteria
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Have a prior history of arterial or venous thrombosis. 2. Participants with a known congenital or acquired thrombophilia with or without thrombosis.
a. Common congenital thrombophilias: i. Protein C deficiency ii. Protein S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv. Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii. Anti-cardiolipin antibodies/Beta2 glycoprotein antibodies iii. Antiphospholipid syndrome
Exclusion Criteria Acquired thrombophilia secondary to medications (birth control pills or hormone replacement therapy), overweight or obesity, smoking, cancer, pregnancy, surgery, injury, prolonged inactivity/bedrest, heart failure, inflammatory bowel disease, or kidney disease
Non-Neoplastic Hematologic Conditions Cohort
Inclusion Criteria
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Having any congenital or acquired non-neoplastic hematologic disorder not included in any other cohort
Exclusion Criteria None
Arm/Module Participant Selection
Previously Untreated Patients Arm
Inclusion Criteria:
• Diagnosis of congenital hemophilia A (FVIII \<40%) or hemophilia B (FIX \<40% or below lower limit for age)
• Age \<18 years at time of enrollment
• Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent
• Care established at one of the ATHN Transcends participating HTCs
• Clotting Factor Concentrate (CFC) exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets \<3 exposure days (ED) Exclusion Criteria
• Concomitant diagnosis with another bleeding disorder
• History of a confirmed, positive inhibitor INHIBIT Module
Inclusion Criteria:
1\. Diagnosis of severe factor VIII deficiency with baseline factor VIII level \<1% 2. Initiating or plan to initiate prophylaxis with emicizumab or factor replacement 3. Factor concentrate exposure, Fresh Frozen Plasma (FFP), cryoprecipitate, and single donor platelets ≤3 EDs 4. ≤5 years of age
Exclusion Criteria
• Concomitant diagnosis with bleeding disorder other than hemophilia A
• Immune disorder
• Previous history or presence of factor VIII inhibitor. A confirmed, positive inhibitor is defined as two consecutive positive inhibitor titers (≥ 0.6 BU) that result in changes in treatment recommendations. Efanesoctocog alfa (ALTUVIIIO®) Module Inclusion criteria:
• Ability of the potential participant's legally authorized representative (e.g., their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulation.
• People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists \<5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of \<1%.) Other severities may be included per ATHN Transcends PI approval.
• \<18 years of age.
• No history of a confirmed, positive FVIII inhibitor.
• Sex assigned at birth of male, female, or intersex.
• Participants should have no more than three (3) exposure days of blood products (fresh frozen plasma, cryoprecipitate, or platelets), no more than three (3) doses of any FVIII concentrate other than efanesoctocog alfa, and up to three (3) doses of efanesoctocog alfa prior to enrollment.
• Site PI confirmed all inclusion criteria has been met. Exclusion criteria:
• Not meeting all the inclusion criteria; confirmed by site PI.
• Any exposure to blood products or FVIII replacement products except as described in the inclusion criteria.
• History of positive inhibitor testing.
• History of hypersensitivity reactions associated with efanesoctocog alfa administration.
• Other coagulation disorder(s) in addition to Hemophilia A.
• Any concurrent clinically significant major disease such as cancer that, in the opinion of the investigator, would make the participant unsuitable for enrollment.
• Concurrent systemic treatment with chemotherapy and/or other immunosuppressant medications. Use of corticosteroids for the treatment of asthma or management of acute allergic or otherwise life-threatening episodes is allowed except for systemic corticosteroid treatment given to children daily or on an alternate day schedule at \> 2 mg/kg/day of prednisone or its equivalent or \> 20 mg/day if the duration is longer than 14 days.
• Enrollment in a concurrent clinical interventional drug study.
• Intake of an Investigational Medicinal Product within three (3) months prior to inclusion in this study.
• Inability to comply with study requirements.
• Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment. Hemophilia Natural History Arm Inclusion Criteria
• Congenital or acquired hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility, OR
• Females of any age, with confirmed congenital hemophilia A or B carrier status with genetic mutational analysis and any factor level. Exclusion Criteria
• Presence of any known bleeding disorder other than congenital hemophilia A or B
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded)
• Unable or unwilling to comply with the study arm protocol. Nonacog beta pegol (Rebinyn®) Module
Inclusion Criteria:
• Has provided signed written consent for the nonacog beta pegol (Rebinyn®)Module before any study-related activities.
• Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment. Additional doses may be allowable per ATHN Transcends PI approval.
• Decision to initiate continuous prophylaxis treatment with commercially available nonacog beta pegol has been made by the participant(s)/Legally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.
Exclusion Criteria:
• Previous participation in this study. Participation is defined as having given informed consent in this study.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.
• Known or suspected hypersensitivity to nonacog beta pegol or related products.
• Clinical suspicion or presence of FIX inhibitor at time of inclusion.
• Inability or unwillingness to undergo neurological assessment/structured developmental history. Emicizumab (Hemlibra®) Module
Inclusion Criteria:
• Participant currently treated with emicizumab (Hemlibra®)
• Currently enrolled in the Hemophilia Natural History Arm of ATHN Transcends
Exclusion Criteria:
1\. Unable or unwilling to comply with the protocol
Distress Module
Inclusion Criteria:
• Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility
• Age 18 years of age or older
• English speaking
Exclusion Criteria:
• Presence of any known bleeding disorder other than congenital hemophilia A or B;
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded); and
• Unable or unwilling to comply with the study arm protocol Hemophilia Gene Therapy Outcomes Arm Inclusion Criteria
• Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.
• Age 18 years and older.
• Able to give informed consent. Exclusion Criteria None Etranacogene dezaparvovec (HEMGENIX®) Module
Inclusion Criteria:
Etranacogene dezaparvovec (HEMGENIX®) Cohort
• Age 18 years of age or older
• Treatment with commercial etranacogene dezaparvovec (HEMGENIX®)
• Have provided signed written informed consent within 3 months before or within 6 months after etranacogene dezaparvovec (HEMGENIX®) treatment, or within 6 months of when the study is initiated at the treating site. FIX Prophylaxis Cohort
• Age 18 years of age or older
• Treatment with FIX prophylaxis therapy
• Has provided signed written consent at any time for ATHN Transcends Study Exclusion Criteria, both cohorts: 1\. Have been treated with etranacogene dezaparvovec in a clinical trial prior to commercial availability. These patients are still eligible for enrollment in the Gene Therapy Outcomes Arm, and their data may be collected for separate analysis. Congenital Platelet Disorders Arm Inclusion Criteria
• Platelet adhesion defect
• Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to vWF)
• Velocardio-facial syndrome/DiGeorge syndrome (Defective GPIb-IX-V receptor)
• Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between vWF-GP1bα)
• Platelet aggregation defect
• Glanzmann thrombasthenia (Defective integrin αIIbβ3 (GPIIb/IIIa)
• Platelet aggregation defect, NOS
• Agonist receptor defects
• Epinephrine
• ADP
• Collagen
• Thromboxane A2
• Platelet signaling defects
• Cyclooxygenase deficiency (PTGS1 mutation)
• Phospholipase A2 deficiency
• Thromboxane synthase deficiency (TBXAS1 mutation)
• G protein activation defect (GNAS mutation)
• Scott syndrome (defect in phosphatidyl serine translocation)
• Platelet Granule disorders
• Dense granule storage pool disorder * Hermansky Pudlak syndrome * Chediak Higashi syndrome * Griscelli syndrome
• Alpha granule storage pool disorder * Grey platelet syndrome * Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome * Quebec platelet disorder * Paris-Trousseau syndrome
• Combined alpha delta granule deficiency
• Platelet cytoskeletal structure defects
• Wiskott Aldrich syndrome
• MYH9 associated disorders (myosin heavy chain) * May Hegglin syndrome * Fechtner syndrome * Sebastian syndrome * Epstein syndrome
• Other mutations * FLNA mutations (Filamin) * DIAPH1 (Actin and microtubules) * ACTN1 (alpha actinin) * TPM4 (tropomyosin) * TUBB1 (beta tubulin)
• Other Congenital thrombocytopenias
• Familial platelet disorders and predisposition to AML (RUNX1)
• X linked thrombocytopenia with dyserythropoiesis (GATA1)
• Congenital amegakaryocytic thrombocytopenia (MPL) Exclusion Criteria
• Diagnosis of von Willebrand Disease (Meeting the definition of vWD or low vWF per most recent international guidelines)
• Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX ≤ 40%) Glanzmann Thrombasthenia (GT) Module Inclusion Criteria
• Participant has signed the informed consent/assent form
• Participant has flow cytometry or aggregometry or genetics confirmed GT
• Participant is willing to perform study procedures, including daily bleed tracking for 3 months and further if requested
• Participants are 2 years or older at time of consent Exclusion Criteria None
Hematologic Disorder, Bleeding Disorder, Connective Tissue Disorder, Hemophilia, Thrombosis, Von Willebrand Diseases, Thrombophilia, Rare Bleeding Disorder, Platelet Disorder, Factor IX Deficiency, Factor VIII Deficiency, Thalassemia, Sickle Cell Disease
Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory Acute Leukemia
Michelle Anton - Michelle.Anton@cchmc.org
ALL
0 years to 21 years old
PHASE1
NCT06376162
Inclusion Criteria:
* Age: 0-21 years (and at least 5 kg body weight), with a minimum of 80% of participants under 18 years of age.
* Diagnosis: KMT2A-r, NPM1-m, or NUP98-r acute leukemia in first or greater relapse or refractory to standard (re-) induction treatment (including HSCT). Please note that genetic alteration must be confirmed by the central laboratory, or the participant will discontinue protocol therapy.
* Eligible participants also must fulfill one of the following conditions:
• Bone marrow relapse is defined as:
• A single bone marrow sample showing ≥ 5% leukemic blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing, or other molecular method. * a single bone marrow sample with at least two tests showing ≥ 1% leukemic blasts, examples of tests (confirmed by central lab) include: Flow cytometry showing leukemia ≥ 1% by multiparameter flow cytometry (MFC) confirmed by central lab. * Karyotypic abnormality as confirmed by central cytogenetic review. * FISH abnormality identical to one present at diagnosis (must be above level of sensitivity of specific FISH probe; central cytogenetic review required). * Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of validated leukemogenic lesion (e.g., fusion, mutation) in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory that matches initial diagnosis and is quantifiable as ≥1% confirmed by central lab.
• Participants with combined extramedullary and bone marrow relapse (defined as above) are eligible.
• Participants with isolated extramedullary disease (EMD) are not eligible. EMD relapse is defined as biopsy-proven extramedullary disease without bone marrow disease after documented complete response (CR) following initial therapy. Participants with isolated central nervous system (CNS) relapse are not eligible. Participants with a combined medullary/extramedullary relapse, including CNS disease, are eligible.
• Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse.
• For participants unable to undergo bone marrow assessment, a peripheral blood absolute blast count ≥ 1,000 cell/microliter is sufficient to diagnose relapsed or refractory disease and facilitate confirmation of required genetic alterations for protocol therapy.
• Refractory disease/induction failure:
• Acute myeloid leukemia (AML): The bone marrow contains ≥ 1% leukemic blasts by MFC at the end of 2 cycles of induction therapy.
• Acute lymphoblastic leukemia (ALL)/mixed-phenotype acute leukemia (MPAL)/acute undifferentiated leukemia (AUL): The bone marrow contains ≥ 1% leukemic blasts by MFC at the end of induction and consolidation, or persistent MRD prior HSCT (defined as \> 0.01%).
• For participants unable to have bone marrow assessed, a peripheral blood absolute blast count ≥ 1,000 cell/microliter is sufficient to diagnose relapsed or refractory disease.
• Molecular refractory disease in infant ALL, defined as MRD \>0.05% after primary induction and consolidation therapy measured by MFC or PCR. * Performance status: Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). Use ECOG for adult participants (≥18 to 21 years), Karnofsky for participants ≥16 to 18 years of age, and Lansky for participants \< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Adequate organ function:
• Renal function defined as: Creatinine clearance (CrCl) ≥60 mL/min (as measured by a nuclear glomerular filtration rate \[GFR\] scan or calculated by the Schwartz formula and normalized to a body surface area of 1.73 m\^2).
• Liver function defined as:
• Direct bilirubin \< 3 x upper limit of normal (ULN) and Serum glutamic pyruvic transaminase (SGPT) (alanine transaminase \[ALT\]) ≤ 5 x ULN.
• If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac function defined as: Pre-treatment left ventricular function on echocardiography: Fractional shortening (FS) ≥ 25% or ejection fraction (EF) ≥ 40%, and no signs of congestive heart failure within 4 weeks before start of screening. * Prior therapy: Participants must have recovered from the acute toxic effects of all prior anti-cancer therapy (excluding Grade 2 toxicities that are not considered a safety risk or medically significant toxicity deemed irreversible by the Investigator) and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
• Cytotoxic chemotherapy: Must not have received within 14 days or within 5 drug half-lives (whichever is longer), of entry onto this study, except for hydroxyurea or corticosteroids. Use of steroids and hydroxyurea for other purposes such as differentiation syndrome, or to premedication to prevent allergic reaction or during anesthesia is allowed.
• Intrathecal cytotoxic therapy: No washout or waiting period is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before enrollment. Any toxicity related to prior antibody therapy must be recovered back to baseline.
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., peg-filgrastim) or 7 days for short-acting growth factor.
• Radiation therapy (RT): 14 days have elapsed for local palliative RT (small port); ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem cell infusions:
• Participants who have relapsed after allogeneic (non-autologous) BM or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) must be at least 84 days post HSCT and without evidence of graft versus host disease (GVHD) of any severity except: the use of topical steroids for cutaneous GVHD is allowed and stable steroid doses less than or equal to 10 mg of prednisone daily is permitted. Prednisone dose must be adjusted for body surface area (BSA) in young children. Physiologic doses of hydrocortisone for participants with adrenal insufficiency is allowed.
• Participants who after relapse and continue to receive cyclosporine, tacrolimus or other agents to treat or prevent either GVHD post BM transplant or organ rejection post-transplant are not eligible for this trial. In the relapse setting, participants must be off medications to treat or prevent either GVHD post BM transplant or organ rejection post-transplant for at least 14 days prior to enrollment. A stable steroid dose as mentioned above is allowed.
• Cellular therapy: ≥ 30 days after the completion of DLI or any type of cellular Therapy (e.g., modified T cells, NK cells, dendritic cells, etc.).
• Prior exposure to a different menin inhibitor: Participants who received previous treatment with a different menin inhibitor are allowed to enrol in the study with the exception of those who experienced a severe adverse event attributable to the strong anti-proliferative/pro-differentiation effects of other menin inhibitors (such as severe differentiation syndrome). Participants who experienced a severe adverse event, which can directly be attributed to specific effects (e.g., long QT syndrome) observed with other menin inhibitors can participate in the study if they fulfill the inclusion criteria. * Informed consent: Written, signed and dated informed consent and pediatric assent (if applicable) according to local law and legislation should be collected before start of any study procedures. * Female participants of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. * Female participants with infants must agree not to breastfeed their infants while on this study. * Contraception:
• Participants of reproductive potential, starting from menarche and onwards, may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. For further guidance please review the CTFG website.
• Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. * Enrollment APAL2020SC trial (US and Canada only): Participants in the US and Canada must have enrolled in the APAL2020SC trial prior to enrollment in the APAL2020K trial.
Exclusion Criteria:
* Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study.
* Participants with Down syndrome.
* Participants with EMD are not eligible. EMD relapse is defined as biopsy proven extramedullary disease without bone marrow disease after documented CR following initial therapy.
* Participants with isolated CNS relapse are not eligible, as well as symptomatic CNS3 disease.
* Participants with acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
* Participants with malabsorption syndrome or any other condition that precludes enteral administration of a menin inhibitor.
* Concomitant therapy: Gastric pH has great influence on absorption of ziftomenib; therefore, the use of proton pump inhibitors is prohibited, if necessary H2 Blockers may provide an alternative treatment option.
* Participants who are currently receiving another investigational drug.
* Participants with any known congenital bone marrow failure syndrome.
* Participants with known prior allergy to any of the medications used in protocol therapy.
* Participants with documented active, uncontrolled infection at the time of study entry.
* Active/uncontrolled known human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) and hepatitis C virus (HCV). Note: HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standard.
* Post menarche female participants with positive pregnancy test, and a lactating female participant.
* Participant has a pre-existing disorder predisposing the participant to a serious or life-threatening infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenia not related to the leukemia or its treatment).
* Participants must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative/herbal therapies) within 30 days of first dose of study drug or while on study.
* Significant congenital cardiovascular disease including, but not limited to conditions such as long QT syndrome, fundamental uncorrected cardiac defect (e.g., coarctation of the aorta) that poses a significant risk to the participant (ventricular septal defect or atrial septal defect are considered non-significant).
* Underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or AEs.
* For fludarabine and cytarabine: Hypersensitivity to the active substance or to any of the excipients.
* Recent live vaccinations for at least 6 months. DRUG: Ziftomenib, DRUG: Cytarabine, DRUG: Fludarabine
Relapsed/Refractory KMT2A-r Acute Leukemia, Relapsed/Refractory NUP98-r Acute Leukemia, Relapsed/Refractory NPM1-m Acute Leukemia
Ziftomenib, Acute leukemia, KMT2A-r, NUP98-r, NPM1-m
Congenital Hemolytic and Dyserythropoietic Anemias
Megan Metcalf - megan.metcalf@cchmc.org
ALL
NCT07649213
Inclusion Criteria:
• Patients who have been diagnosed, by medical history and review of the laboratory data obtained for clinical care, including CBC/reticulocyte count and review of the blood smear, with a hereditary hemolytic anemia, where the genetic etiology is challenging to be identified.
• Parents and/or grandparents of children that have the above diagnosis. The parents and/or grandparents may or may not have non-immune hemolytic anemia (these will serve as positive or negative inherent controls) Exclusion: 1\) Patients with anemias known to be acquired and not associated with a genetic etiology.
Hemolytic Anemia
INTO-HLH: A Disease Registry for Patients With Hemophagocytic Lymphohistiocytosis (HLH)
Brian Hils - brian.hils@cchmc.org
ALL
NCT05277272
Inclusion Criteria:
* Patients with clinically suspected or confirmed HLH, including those meeting the HLH-2004 diagnostic criteria (primary or secondary forms, including malignancy) and other forms of HLH (macrophage activation syndrome \[MAS\], cytokine release syndrome \[CRS\], etc.)
* Signed and dated informed consent and assent (adolescents)
Exclusion Criteria:
* None Hemophagocytic Lymphohistiocytoses
The Congenital Dyserythropoietic Anemia Registry (CDAR)
Theodosia Kalfa - theodosia.kalfa@cchmc.org
ALL
NCT02964494
Inclusion Criteria:
* Diagnosis of Congenital Dyserythropoietic Anemia (CDA), whether a genetic mutation is identified or not
* Evidence of congenital anemia/jaundice or a positive family history
* Evidence of ineffective erythropoiesis
* Typical morphological appearance of bone marrow erythroblasts
* All ages (ages 0-99)
Exclusion Criteria:
* Diagnosis of cancer
* Myelodysplasia
* Secondary dyserythropoiesis: e.g.; vitamin B12 deficiency or drug-related.
Note1: Patients with rare band 3 (SLC4A1) mutations recently described to be associated with dyserythropoiesis will be eligible since the mechanisms appear to involve direct participation of band 3 in the erythroblast mitosis and cytokinesis.
Note2: Siblings, parents, and family members of patients with confirmed CDA diagnosis are encouraged to participate in the study. Congenital Dyserythropoietic Anemia (CDA)
Single Arm Romiplostim to Prevent CIT
- cancer@cchmc.org
ALL
1 year and over
EARLY_PHASE1
NCT07048249
Inclusion Criteria:
* Age: Patients must be \>1 year old at the time of study consent.
* Diagnosis: Patients with a new diagnosis of Ewing sarcoma treated with interval-compressed chemotherapy as per AEWS0031, AEWS1221, or AEWS1031.
* Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
* Marrow disease: Patients with metastatic Ewing sarcoma to the bone marrow are not eligible. Marrow staging is not required for this study but should be performed if clinically indicated.
* Concomitant therapy, cancer directed: Patients receiving whole lung radiation, \>50% of pelvic irradiation, other substantial bone marrow radiation (i.e. ≥ 50% of vertebral marrow space), or patients undergoing pneumonectomy as a component of local control before cycle 14, are not eligible. These therapies are not an exclusion if instituted during or after cycle 14.
* Concomitant therapy, non-cancer directed:
* Patients requiring hematopoietic stem cell rescue are not eligible.
* Previous use of romiplostim, eltrombopag or any other platelet-producing agent is not allowed.
* Previous therapy for immune thrombocytopenia and related conditions, including rituximab, mycophenolic acid, protracted systemic steroids, and/or IVIG, is prohibited.
* Treatment with erythropoietin-stimulating agents is prohibited.
* Patients receiving another investigational drug are not eligible.
* Patients who are receiving prophylactic dosing of heparin (i.e. enoxaparin) or oral anticoagulants (i.e. rivaroxaban) for thrombosis prevention may be considered for enrollment but will be excluded from secondary aim 'a' analysis (efficacy measured as the median platelet count and transfusion dependency) given shift in transfusion thresholds.
* Concurrent Illnesses: Patients with a history of or current diagnosis of bone marrow failure, hematologic malignancy, pro-thrombotic condition, or platelet disorder (including immune or heparin induced thrombocytopenia) are not eligible.
* Patients who in the opinion of the investigator may not be able to comply with the study (including safety monitoring requirements of the study) are not eligible. DRUG: Romiplostim (AMG-531)
Ewings Sarcoma, Chemotherapy Induced Thrombocytopenia
romiplostim, ewing sarcoma, chemotherapy induced thrombocytopenia, CIT, NPLATE
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
cancer@cchmc.org
ALL
1 month to 21 years old
PHASE1
NCT05849662
Inclusion Criteria:
Age
• Patients must be ≥ 1 month and ≤21 years of age at enrollment.
Diagnosis • Patients must meet the 2022 International Consensus Classification criteria for JMML. The diagnosis is made based on the following criteria:.
Clinical and hematologic features (the first 2 features are present in most cases; the last 2 are required):
* Peripheral blood monocyte count ≥ 1 × 109/L\*
* Splenomegaly†
* Blast percentage in PB and BM \< 20%
* Absence of BCR::ABL1
* This monocyte threshold is not reached in approximately 7% of cases. †Splenomegaly is absent in 3% of cases at presentation.
II. Genetic studies (1 finding required):
* Somatic mutation in PTPN11‡ or KRAS‡ or NRAS‡ or RRAS or RRAS2‡
* Clinical diagnosis of neurofibromatosis type 1 or germline NF1 mutation and loss of heterozygosity of NF1 or somatic biallelic loss of NF1
* Germline CBL mutation and loss of heterozygosity of CBL, or somatic mutation(s) in CBL§
* Germline mutations (indicating Noonan syndrome) need to be excluded. §Occasional cases with heterozygous splice site mutations.
Performance Level
* Karnofsky \> 50% for patients ≥ 16 years of age
* Lansky \> 50% for patients \< 16 years of age.
Prior Therapy
* No prior leukemia directed therapy is permitted with the exception of:
• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of trametinib.
• Cytoreduction with 6-mercaptopurine (6-MP) 6-MP can be initiated and continued for up to 72 hours prior to the start of trametinib.
• Intrathecal (IT) cytarabine, IT methotrexate or triple IT therapy (cytarabine, methotrexate and hydrocortisone) within 7 days of enrollment as part of a diagnostic evaluation. No prior hematopoietic stem cell transplant is permitted. Adequate Renal Function Defined as: * Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below: Maximum Serum Creatinine (mg/dL): * 1 month to \< 6 months old - Male: 0.4, Female 0.4 * 6 months to \<1 year old - Male 0.5, Female 0.5 * 1 to \< 2 years old - Male: 0.6, Female: 0.6 * 2 to \< 6 years old - Male:0.8, Female: 0.8 * 6 to \< 10 years old - Male: 1, Female: 1 * 10 to \< 13 years old - Male: 1.2, Female: 1.2 * 13 to \< 16 years old - Male: 1.5, Female: 1.4 * ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) \< 5 x ULN for age. * The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia and will not be evaluable for hepatotoxicity. This must be reviewed and approved by the study chair or vice chair. Adequate Cardiac Function Defined as: * Ejection fraction of \> or = to 50% by echocardiogram, OR * Ejection fraction of \> or = to 50% by radionuclide angiogram (MUGA). Reproductive Function * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
Exclusion Criteria:
* Patients cannot have a known allergy to any of the drugs used in the study.
* Patients cannot have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
* Patients cannot have a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Patients cannot have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
* Patients cannot have a clinical or molecular diagnosis of Noonan syndrome. Note: patients with either neurofibromatosis type 1 or Casitas B-lineage lymphoma (CBL) syndrome (also known as Noonan-like syndrome), are eligible to enroll. Patients with Down syndrome are excluded from the study.
* Patient cannot have had prior use of hematopoietic growth factors, biologics (anti-neoplastic agent), or XRT.
* Patients cannot be taking any medications for treatment of left ventricular systolic dysfunction.
* Patients cannot have a history of or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
* Patients cannot have had prior use of any MEK inhibitor. DRUG: Trametinib, DRUG: Azacitidine, DRUG: Fludarabine, DRUG: Cytarabine
Leukemia, Juvenile Myelomonocytic, JMML, JCML, Neurofibromatosis 1, CBL Syndrome
Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation
Caitlin Cottrell - caitlin.cottrell@cchmc.org
ALL
PHASE2
NCT05501756
Inclusion Criteria:
* Patients who are undergoing allogeneic HCT at CCHMC with an alemtuzumab-containing preparative regimen for treatment of a non-malignant disease are eligible.
* For the first 7 patients, patients must have a 10/10 HLA matched related or unrelated stem cell donor, or be receiving a CD34+ selected stem cell product. After the first 7 patients, any donor match may be allowed after data review by the BMT clinicians and the PI.
Exclusion Criteria:
* Patients with a history of anaphylaxis to alemtuzumab.
* Patients who have previously received alemtuzumab and have not cleared alemtuzumab prior to the start of the preparative regimen.
* Life expectancy less than 4 weeks.
* Patients receiving dialysis or plasmapheresis at the time of the start of the conditioning regimen.
* Failure to sign informed consent and/or assent, or inability to undergo informed consent process.
* It is not medically advisable to obtain the specimens necessary for this study.
* Not able to tolerate subcutaneous dosing (patients with severe skin conditions).
* Patients with cancer.
* Patients whose clinical condition suggest there may be inability to successfully perform the PK modeling such as, but not limited to, active flaring of hemophagocytic lymphohistiocytosis in which excessive lymphoproliferation may significantly alter the target-mediated clearance of alemtuzumab and prevent observation of non-target mediated clearance which is needed for robust modeling.
* Patients whose pre-alemtuzumab level reveals an interfering substance which prevents accurate measurement of alemtuzumab. DRUG: Alemtuzumab
Allogeneic Hematopoietic Cell Transplantation
Quercetin in Patients With XIAP (X-linked Inhibitor of Apoptosis) Deficiency
Kelly McIntosh - Kelly.mcintosh@cchmc.org
MALE
2 years and over
PHASE1
NCT07433621
Inclusion Criteria:
* Male patients
* Diagnosis of XIAP deficiency
* Patients ≥2 years of age
* Serum IL-18 ≥600 pg/mL (approximately 25% above the lab-defined upper limit of normal of 477 pg/mL)
* Able to take enteral medication
Exclusion Criteria:
* Renal failure requiring dialysis
* Total bilirubin \>3 mg/dl and/or SGPT \>300 at time of enrollment
* Patients receiving digoxin therapy, who are unable to discontinue treatment due to medical reasons
* Patients receiving fluoroquinolone therapy, who are unable to discontinue treatment due to medical reasons
* Patients who are at risk of pregnancy or fathering a child and are unable to use acceptable methods of birth control during the length of the study
* Patients who have received quercetin or any over the counter anti-oxidant supplementation within last 1 month
* Patients with unstable disease status or other medical issues requiring hospitalization or rapid escalation of medical care
* Participating in another therapeutic study for XIAP deficiency DRUG: Quercetin
XIAP Deficiency
Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
- cancer@cchmc.org
ALL
1 year to 30 years old
PHASE1
NCT06177067
Inclusion Criteria:
Participants must have a diagnosis of AML or ALAL and meet the criteria below:
* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.
However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214
* Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
* QTcF \< 480 msec (average of triplicate)
* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
* Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
* Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.
Exclusion Criteria:
* Patients who are pregnant or breastfeeding are not eligible.
* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible. DRUG: Cytarabine, DRUG: Methotrexate, DRUG: Revumenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: intrathecal (IT) chemotherapy
Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage
Minima Stent System Post- Approval Study (PAS)
Amy Amy Pajk - Amy.Pajk@cchmc.org
ALL
NCT06828770
Inclusion Criteria:
* The subject's legally authorized representative has been informed of the nature of the device treatment, agrees to its provisions, and has provided written informed consent
* Indicated for treatment with the Minima Stent System per the IFU.
Exclusion Criteria:
* Active bloodstream infection requiring antibiotic therapy within 3 days prior to stent implantation
* History of or active endocarditis (active treatment with antibiotics) within 180 days prior to stent implantation
* Aortic or pulmonary artery aneurysm in the location targeted for treatment
* Body weight \< 1.5 kg
* Anatomic location of lesion judged by the investigator to not lend to the safe placement of a stent
* Target vessels larger or smaller than the Minima System balloon size ranges
* Known genetic syndrome known to be associated with vasculopathies such as but not limited to Williams syndrome, Loeys-Dietz syndrome, etc
* Clinical scenario requiring that more than one vessel needs stent implantation at the time of the trial procedure.
* Currently participating in an investigational drug study or another device study
* Major or progressive non-cardiac disease resulting in a life expectancy of less than six months
* Known hypersensitivity to aspirin or heparin and cannot be treated with other antiplatelet and/or antithrombotic medications
* Known hypersensitivity to cobalt-chromium or contrast media that cannot be adequately premedicated DEVICE: Minima Stent System
Pulmonary Artery Stenosis, Aortic Coarctation
Vascular Stenosis, Minima, Minima Stent, Minima Stent System, Renata Medical, Renata, infant stent
Prevention of Graft Rejection in Hematopoietic Stem Cell Transplant (HSCT) Recipients
Jessica Anderson - jessica.anderson@cchmc.org
ALL
EARLY_PHASE1
NCT07244419
Inclusion Criteria:
* All patients undergoing allogeneic HSCT at our institution will be evaluated for graft rejection risk factors. Patients deemed high risk for graft rejection will have 2 or more of the following: mismatched or haploidentical donor, ex vivo t-cell depleted graft, prior history of graft rejection.
Exclusion Criteria:
* Known hypersensitivity to any constituent of the study medication. DRUG: Emapalumab 3 mg/kg, DRUG: Emapalumab 10 mg/kg
Hematopoietic Stem Cell Transplantation, Graft Failure
Zoledronate to Prevent Bone Health Complications in Pediatric Hematopoietic Stem Cell Transplant Survivors
Jessica Anderson - jessica.anderson@cchmc.org
ALL
5 years to 18 years old
PHASE1
NCT07375290
Inclusion Criteria:
* Patients ≥5 and ≤18 years old who are preparing for HSCT with a height-for-age corrected DXA Z-score of \<-2.0 and admitted to a CCHMC inpatient unit.
* Patients ≥5 and ≤18 years old recovering from HSCT and who have developed de novo acute or chronic GVHD and are admitted to a CCHMC inpatient unit.
Exclusion Criteria:
* Age \<5 years and \>18 years
* Patients with Fanconi anemia or other radiation-sensitive syndromes with increased malignancy risk
* history of prior bisphosphonate use
* low 25-OH vitamin D levels (\<20 ng/mL)
* active febrile illness
* uncontrolled infection
* Elevated creatinine at the time of enrollment, history or renal failure, or documented low glomerular filtration rate (GFR≤90)
* Active bone disease including history of abnormal PTH level for any reason, active bone fracture/healing, or primary disorder of bone development or metabolism.
* Women who are pregnant or breast feeding. DRUG: Zoledronate
Hematopoietic Stem Cell Transplantation
Zinc Supplementation in Sickle Cell Disease: A Precursor to the Think Zinc for Bones Trial (ZnSCD)
Amy Shova - Amy.Shova@cchmc.org
ALL
15 years to 40 years old
PHASE2
NCT06260891
Inclusion Criteria:
* Age: ≥ 15.0 to ≤ 40.0 years
* Diagnosis: SCD-SS or SCD-S Beta zero Thalassemia, in steady state (defined as a minimum of 2 weeks days following pain crisis)
* Male or Female
Exclusion Criteria:
* Taking any supplement containing zinc and unable/willing to stop for 3 months prior to study start
* 25-Hydroxy Vitamin D \< 20 ng/mL
* On chronic transfusion therapy (defined as \>8 Transfusions/year) and iron overloaded (defined as liver iron concentration \> 7 mg/g OR average serum ferritin \>4000 ug/L)
* Unable swallow pills or take daily supplement as instructed
* Currently participating in another investigational drug trial
* Prior diagnosis of chronic kidney disease (eGFR \< 30 mL/min/1.73m2) DRUG: 25 mg/day zinc, DRUG: 40 mg/day zinc
Sickle Cell Disease
A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections
Joan Moore - Joan.Moore@cchmc.org
ALL
12 years and over
PHASE3
NCT06056297
Key
• Isolated with a permanent (non-cyclic) presentation, for example, elastase, neutrophil expressed (ELANE), colony stimulating factor 3 receptor (CSF3R), C-X-C chemokine receptor 2 (CXCR2), Wiskott-Aldrich syndrome (WAS)
• Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
• Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
• Shwachman-Diamond syndrome * Acquired Primary Neutropenia
• Chronic idiopathic neutropenia
• Primary autoimmune neutropenia. Other chronic neutropenia (CN) disorders that may be eligible for enrollment can be clarified and approved upon discussion with study Medical Monitor. * Have an ANC \<1000 cells/µL during screening (single ANC value from hematology) and confirmed trough mean ANC (mean value of multiple ANC measurements over 6 hours) at baseline visit, with no clinical evidence of systemic infection. * Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet the following criteria: * Infection requiring the use of antibiotics (intravenous \[IV\]/oral); OR * Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician's office, or in-patient hospitalization); AND for all potential participants: * Infections considered by the Investigator to be likely related to the potential participant's CN disorder. * Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC \>10,000 cells/µL for ≥4 weeks). * Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study. Key
• Hypersplenism
• Infection
• Malignancy
• Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
• Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
• Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies. * A diagnosis of any of the following:
• Aplastic anemia
• Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
• Certain CNs, including but not limited to these classifications are excluded:
• Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
• Associated with immune dysregulation, for example, common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA-binding protein 2 (GATA2) deficiency syndrome
• Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia
• Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia). However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion * A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participant's successful completion of the clinical study, or could, in the opinion of the Investigator or the Medical Monitor, interfere with the objectives of the study. * Received more than 1 dose of mavorixafor in the past. * Received C-X-C chemokine receptor 4 (CXCR4) antagonist (other than mavorixafor) in the past 6 months. * Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening. * Participant is currently taking or has taken other investigational drug \<30 days prior to the screening visit or 5 half-lives, whichever is longer. Note: Other protocol-defined inclusion and exclusion criteria may apply.
Inclusion Criteria:
* Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder ≥6 months prior to the screening visit that is not attributable to medications, active or recent infections or malignancy.
* Congenital Neutropenia, including but not limited to these classifications:
• Isolated with a permanent (non-cyclic) presentation, for example, elastase, neutrophil expressed (ELANE), colony stimulating factor 3 receptor (CSF3R), C-X-C chemokine receptor 2 (CXCR2), Wiskott-Aldrich syndrome (WAS)
• Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
• Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
• Shwachman-Diamond syndrome * Acquired Primary Neutropenia
• Chronic idiopathic neutropenia
• Primary autoimmune neutropenia. Other chronic neutropenia (CN) disorders that may be eligible for enrollment can be clarified and approved upon discussion with study Medical Monitor. * Have an ANC \<1000 cells/µL during screening (single ANC value from hematology) and confirmed trough mean ANC (mean value of multiple ANC measurements over 6 hours) at baseline visit, with no clinical evidence of systemic infection. * Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet the following criteria: * Infection requiring the use of antibiotics (intravenous \[IV\]/oral); OR * Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician's office, or in-patient hospitalization); AND for all potential participants: * Infections considered by the Investigator to be likely related to the potential participant's CN disorder. * Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC \>10,000 cells/µL for ≥4 weeks). * Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study. Key
Exclusion Criteria:
* A diagnosis of secondary neutropenia including those due to:
• Hypersplenism
• Infection
• Malignancy
• Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
• Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
• Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies. * A diagnosis of any of the following:
• Aplastic anemia
• Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
• Certain CNs, including but not limited to these classifications are excluded:
• Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
• Associated with immune dysregulation, for example, common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA-binding protein 2 (GATA2) deficiency syndrome
• Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia
• Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia). However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion * A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participant's successful completion of the clinical study, or could, in the opinion of the Investigator or the Medical Monitor, interfere with the objectives of the study. * Received more than 1 dose of mavorixafor in the past. * Received C-X-C chemokine receptor 4 (CXCR4) antagonist (other than mavorixafor) in the past 6 months. * Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening. * Participant is currently taking or has taken other investigational drug \<30 days prior to the screening visit or 5 half-lives, whichever is longer. Note: Other protocol-defined inclusion and exclusion criteria may apply.
DRUG: Mavorixafor, DRUG: Placebo
Neutropenia
Mavorixafor, Chronic neutropenia, Chronic idiopathic neutropenia, Severe Congenital Neutropenia (SCN), C-X-C chemokine receptor 4 (CXCR4), Congenital and acquired neutropenia, Autoimmune disease, Cohen syndrome, Barth syndrome, ELANE, G6PC3, GSD1b, Kostmann disease, Shwachman-Diamond syndrome, Autoimmune neutropenia (AIN)
Quercetin Dyskeratosis Congenita (DC)/Telomere Biology Disorders (TBD)
Stephanie Edwards - stephanie.edwards@cchmc.org
ALL
2 years and over
PHASE1
NCT07628972
Inclusion Criteria:
• Diagnosis of DC/TBD deficiency as defined by at least one of the following: * Age adjusted mean-telomere length of \<1 percentile in all tested peripheral blood cells such as granulocytes, lymphocytes, B-cells, naïve T-cells, memory T-cells, and NK cells * A pathogenic or likely pathogenic mutation in DKC1, TERC, TERT, NOP10, NHP2, TINF2, CTC1, PARN, RTEL1, ACD, NAF1, ZCCHC8, or WRAP53
• Patients ≥ 2.0 years of age\* * The first three enrolled patients must be ≥ 10.0 years of age
• Able to take medication orally
Exclusion Criteria:
• Renal failure requiring dialysis
• Total bilirubin \>3 mg/dl and/or SGPT \>300 at time of enrollment, unless elevation thought to be related to DC/TBD
• Patients who have received quercetin or any over-the-counter antioxidant supplementation within last 1 month
• Patients currently taking androgen therapy
• Patients receiving digoxin therapy, who are unable to discontinue treatment due to medical reasons
• Patients receiving fluoroquinolone therapy, who are unable to discontinue treatment due to medical reasons
• Patients who are pregnant or breastfeeding or are at risk of pregnancy and are unable to use acceptable methods of birth control during the length of the study
• Patients with morphologic or cytogenetic evidence of myelodysplasia or leukemia.
• Patients needing to start or actively receiving radiation therapy, chemotherapy or immunotherapy for treatment of SCC or other cancers.
• Patients with unstable disease status or other medical issues requiring hospitalization or rapid escalation of medical care
• Participating in another therapeutic study for DC/TBD
• Patients who are in the early post-stem cell transplant period (i.e. first 6 months post-transplant)
DRUG: Quercetin
Dyskeratosis Congenita, Telomere Disease
Neonatal Platelet Transfusion Threshold Trial (NeoPlaTT)
Traci Beiersdorfer - traci.beiersdorfer@cchmc.org
ALL
1 hour to 48 hours old
NA
NCT06676904
Inclusion Criteria:
* Gestational age of 23 0/7 to 26 6/7 weeks
* Postnatal age of \< 48 hours
Exclusion Criteria:
* Comfort care or withdrawal of care planned
* Neonatal alloimmune thrombocytopenia or suspected/confirmed congenital platelet or bleeding disorder
* Receipt of platelet transfusion
* No receipt of Vitamin K
* Parents/guardian decline consent PROCEDURE: Higher Platelet Transfusion Threshold, PROCEDURE: Lower Platelet Transfusion Threshold
Thrombocytopenia, Neonatal, Platelet Transfusion, Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age, Thrombosis
platelet transfusion, neonatal, thrombosis
Multi-Center Molecular Diagnosis and Host Response of Respiratory Viral Infections in Pediatric Transplant Recipients
Lara Danziger-Isakov, MD - Lara.Danziger-Isakov@cchmc.org
ALL
Up to 18 years old
NCT05550298
Recipient Inclusion Criteria
* Less than 18 years at the time of anticipated transplant
* Participant meets one of the following criteria:
• scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or
• Scheduled to or received solid organ transplant within 7 days before or after enrollment * Participant is receiving care at the time of enrollment at one of the study participating institutions. * Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria * Donor for HCT recipient enrolled on the VIPER study. * Willing and able to provide informed consent.
• scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or
• Scheduled to or received solid organ transplant within 7 days before or after enrollment * Participant is receiving care at the time of enrollment at one of the study participating institutions. * Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria * Donor for HCT recipient enrolled on the VIPER study. * Willing and able to provide informed consent.
Exclusion Criteria:
Recipient Exclusion Criteria
None
Donor Exclusion Criteria
* Is not an HCT donor for a participant enrolled on the VIPER study.
* Not available to provide pre-transplant research blood sample. Hematopoietic Cell Transplant, Solid Organ Transplant, Respiratory Viral Infection
Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies
Charles Alexander - Charles.Alexander@cchmc.org
ALL
1 year to 21 years old
PHASE1
NCT05476770
Inclusion Criteria:
Age
* Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment.
Diagnosis
* Relapsed and/or refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma).
* Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution.
Disease Status:
Monotherapy, Part 1
* Second or greater relapse; or
* Refractory after 2 or more chemotherapy cycles; or
* First relapse after primary chemotherapy-refractory disease; or
* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
Combination therapy, Part 2
* First or greater relapse; or
* Refractory after 2 or more chemotherapy cycles; or
* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
For relapsed/refractory leukemia, patients must have:
* \>5% blasts in the bone marrow aspirate or biopsy by morphology or flow cytometry
* Patients with 1% - 5% blasts are eligible for Part 2, Cohort C (only), if A single bone marrow sample with flow cytometry and at least one other test (e.g. karyotype, FISH, PCR, or NGS) shows ≥ 1% leukemic blasts and/or flow cytometry demonstrates a stable or rising level of disease on two serial bone marrows.
For relapsed/refractory non-Hodgkin or Hodgkin lymphoma, patients must have:
* Histologic verification of relapse
* Measurable disease documented by radiographic criteria or bone marrow
* Patients in Part 1 may have sites of non-CNS extramedullary disease, but no CNS disease. Patients in Part 2 may have CNS disease and/or other non-CNS extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
* Patients with Down syndrome are eligible to participate in Part 1 only.
Performance Level
* Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age (See Appendix I for Performance Scales). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Prior Therapy
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria.
Myelosuppressive chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 day must have elapsed since the completion of myelosuppressive therapy. However, individuals may receive any of the following medications within 14 days without a "wash-out period":
* Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
* "Maintenance-style" therapy: therapy including vincristine (dosed a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed a maximum of one-time weekly), intrathecal therapy (dosed a maximum of one-time weekly) and/or dexamethasone (dosed at ≤3 mg/m2/dose twice daily) or prednisone (dosed at ≤20 mg/m2/dose twice daily) can be continued for up to 24 hours prior to entering the study.
* Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
* Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
* Monoclonal antibodies: Maximum of 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody.
* Immunotherapy: At least 30 days from last infusion of chimeric antigen receptor T cell (CART) therapy or tumor vaccine.
* Radiation Therapy (XRT):
• ≥ 84 days must have passed, from the end of therapy, if patient received prior total body irradiation (TBI).
• ≥ 42 days must have passed, from the end of therapy, if patient received craniospinal irradiation (CSI).
• ≥ 14 days must have passed after whole brain radiotherapy or stereotactic radiation therapy.
• No washout period is required for: i. Extramedullary site other than CNS that is a maximum 10 x 10 cm total radiation non-CNS field. If the field is \> 10 x 10 cm, a 14-day washout period is required. ii. Local ocular radiotherapy as long as subject has measurable/evaluable disease outside the radiation port. * Patients that have received other non-tagraxofusp CD123 targeting agents are eligible. Patients that have previously received tagraxofusp are not eligible. Organ Function Requirements Adequate Bone Marrow Function Defined as: * Patients should not be known to be refractory to red blood cell or platelet transfusions. * Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be ≥20,000/mm3 to initiate therapy (may receive platelet transfusions). Adequate Renal Function Defined as: * Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below: Maximum Serum Creatinine (mg/dL): * 1 to \< 2 years old - Male: 0.6, Female: 0.6 * 2 to \< 6 years old - Male:0.8, Female: 0.8 * 6 to \< 10 years old - Male: 1, Female: 1 * 10 to \< 13 years old - Male: 1.2, Female: 1.2 * 13 to \< 16 years old - Male: 1.5, Female: 1.4 * ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined as: * Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x institutional upper limit of normal for age * SGPT (ALT) and SGOT (AST) must be less than 3x institutional upper limit of normal. * Serum albumin ≥3.2 g/dL (albumin infusion independent). Adequate Cardiac Function Defined as: * Shortening fraction of ≥27% by echocardiogram, or * Ejection fraction of ≥ 50% by gated radionuclide study/echocardiogram. Adequate Pulmonary Function Defined as: * Pulse oximetry \> 94% on room air (\> 90% if at high altitude) * No evidence of dyspnea at rest and no exercise intolerance. Reproductive Function * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 12 weeks after the last dose of tagraxofusp. Exclusion Criteria Disease Status: * Patients with CNS disease are not eligible for Part 1. * Patients with isolated CNS disease are not eligible for Part 1 or Part 2. * Patients with isolated non-CNS disease are eligible for Part 1 and Part 2. Concomitant Medications * Corticosteroids - Patients receiving corticosteroids for disease control who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. * Investigational Drugs - Patients who are currently receiving another investigational drug are not eligible. The definition of "investigational" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia) * Anti-cancer Agents - Patients who are currently receiving or may receive while on therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible \[with the exceptions being laid out in the inclusion criteria under 'Prior Therapy'\]. Intrathecal chemotherapy (at the discretion of the primary oncologist) may be given up to one week prior to the initiation of study treatment (day 1 therapy). * Anti-GVHD or agents to prevent organ rejection post-transplant - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 4 weeks must have elapsed after the last dose of GVHD meds. Infection Criteria - Patients are excluded if they have: * Positive blood culture within 48 hours of study enrollment; * Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability. * A positive fungal culture within 30 days of study enrollment. * Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed. * Patients will be excluded if they have a known allergy to any of the drugs used in the study. * Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results. * Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
DRUG: Tagraxofusp, DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Dexamethasone, DRUG: Vincristine, DRUG: Azacitidine, DRUG: Methotrexate, DRUG: Cytarabine IT, DRUG: Hydrocortisone
Hematologic Malignancy, AML, ALL, BPDCN, MDS, Lymphoblastic Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell, Hodgkin Lymphoma, Mixed Phenotype Acute Leukemia, Acute Undifferentiated Leukemia
Project: Every Child for Younger Patients With Cancer
- cancer@cchmc.org
ALL
Up to 25 years old
NCT02402244
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal Neoplasm
Donor-Derived Viral Specific T-cells (VSTs) (VSTs)
Jamie Wilhelm - Jamie.Wilhelm@cchmc.org
ALL
1 month(s) and over
PHASE1
NCT02048332
Inclusion Criteria:
* Recipient must be at least 21 days after stem cell infusion
* Clinical status must allow tapering of steroids to 0.5mg/kg prednisone or other steroid equivalent
* Recipient must have achieved engraftment with ANC ≥ 500
Exclusion Criteria:
* Active acute GVHD grades II-IV
* Uncontrolled bacterial or fungal infection
* Uncontrolled relapse of malignancy requiring treatment with chemotherapy
* Infusion of ATG or alemtuzumab within 2 weeks of VST infusion BIOLOGICAL: Viral specific VST Infusion
Allogeneic Stem Cell Transplant, Viral Infection, Viral Reactivation
Epstein-Barr Virus (EBV), Adenovirus (ADV), t-cells, donor, transplant, children, cytomegalovirus (CMV), BK virus (BKV)
Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation (HELPFUL)
Teresa Latham - Teresa.Latham@cchmc.org
ALL
NCT04093986
Inclusion Criteria:
* Medical records or data available from previous clinical care prior to June 20, 2019 of pregnant females with SCD, including women who miscarried, had a still birth, or completed labor at any gestational stage, with any hydroxyurea exposure during either pregnancy and/or while breastfeeding.
* Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.
Exclusion Criteria:
* Unavailable medical records or lack of information about hydroxyurea exposure. OTHER: Chart Review, OTHER: Survey
Sickle Cell Disease, Sickle Cell Anemia
Hydroxyurea