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340 Study Matches
Quantifying Motor Network Dynamics to Predict and Enhance Outcomes in Pediatric Dystonia
Karlee Migneault - karlee.migneault@cchmc.org
ALL
6 years to 21 years old
NA
NCT07325175
Inclusion Criteria:
* For dystonia subjects:
* Dx of dystonia (with and without DBS)
* willingness and ability to complete study protocols.
* For Typically Developing Controls:
* normal developmental milestones
* absence of any neuropsychiatric disorder
* no significant medical condition.
Exclusion Criteria:
* history of epilepsy
* presence of implanted medical devices (except DBS in dystonia subjects)
* lack of cognitive or physical ability to complete study protocol. DEVICE: DBS
Dystonia, Pediatric, Deep Brain Stimulation, Motor Development
A Research Study to Advance the CF Therapeutics Pipeline for People Without Modulators
Kelly Thornton - Kelly.Thornton@cchmc.org
ALL
12 years and over
NCT06504589
Consent
A. Written informed consent (and assent when applicable) obtained from participant or participant's legal guardian
B. Is willing and able to adhere to the study visit schedule and other protocol requirements
Demographics
A. ≥ 12 years of age at Visit 1
Medical History
A. For persons of child-bearing potential: must not be pregnant at Visit 1 or plan to get pregnant during the 12-month study period
Disease History
A. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
* Sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
* Two well-characterized disease-causing pathogenic variants in the CFTR gene
or
* One well-characterized disease-causing mutation and a second CFTR variant (with variable or uncharacterized disease-causing potential) and sweat ≥ 30 mmol/liter with permission of the study sponsor-investigators
B. Clinically stable with no significant changes in health status within the 28 days prior to and including Visit 1
C. Does not have a history of lung transplantation
Concomitant Medications
A. Not genetically eligible for a CFTR modulator according to product label indications and/or No use of CFTR modulator for 28 days prior to Visit 1 with no intent to start or restart during the study period
B. No use of an investigational drug within 90 days prior to and including Visit 1
C. Not currently participating in an interventional drug or device trial. Participation in long-term safety follow-up studies (without redosing) and/or behavioral intervention trials is allowed.
D. No initiation of new chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, Cayston®) within 28 days prior to and including Visit 1
E. No acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 28 days prior to and including Visit 1
Cystic Fibrosis
ineligible and/or not taking CFTR modulators, People with CF
Pulmonary Hypertension Association Registry (PHAR)
Jaynee Bartsch - jaynee.bartsch@cchmc.org
ALL
Not specified
NCT04071327
Inclusion Criteria:
* All age groups
* Written informed consent
* Pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), or pediatric PH due to developmental lung disease
* Within 6 months of first outpatient visit at a PH Care Center
Exclusion Criteria:
* Diagnosis of WSPH Group 2 pulmonary hypertension
* Diagnosis of WSPH Group 3 pulmonary hypertension, except PH due to developmental lung disease
* Diagnosis of WSPH Group 5 pulmonary hypertension Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Hypertension
Haploidentical Donor Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Relapsed & Refractory Neuroblastoma
- cancer@cchmc.org
ALL
1 year to 39 years old
PHASE2
NCT07635056
Inclusion Criteria:
* Age 1-39 years at the time of study enrollment
* With diagnosis of neuroblastoma with histologic verification
* Classified as high-risk neuroblastoma as defined by Children's Oncology Group (COG) risk classification, including patients initially classified as low or intermediate risk at diagnosis with subsequent reclassification as high-risk disease
* With relapsed or refractory disease, including at least one of the following:
• Recurrent disease at any time after completion of frontline therapy
• Progressive disease at any time following standard induction therapy
• Primary resistant or refractory disease defined by failure to achieve a complete response by International Neuroblastoma Response Criteria (INRC) after at least four cycles of standard, multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol * Patients must have evaluable disease documented within four weeks of study enrollment. Evaluable disease must include at least one of the following:
• Measurable tumor (\>10 mm in at least one dimension) on MRI or CT scan that is either MIBG, FDG or 68Ga-DOTATATE avid
• One or more MIBG, FDG, or 68Ga-DOTATATE avid bone lesion
• Microscopic marrow metastasis based on routine morphology and/or immunohistochemistry in at least one sample from bilateral aspirates and biopsies at the time of study enrollment. * With performance level of \>50% on Lansky (\<16 years) or Karnofsky (\>16 years) scales. Patients who are wheelchair bound due to paralysis will be considered ambulatory when assessing their performance score. * Adequate baseline cardiac and pulmonary function including a left ventricular ejection fraction (LVEF) \>50% by echocardiogram and pulse oximetry \>92% on room air documented within four weeks of study enrollment. * Adequate baseline hematologic function: peripheral absolute neutrophil count (ANC) ≥500/µL, with no receipt of long-acting myeloid growth factors within 14 days or short-acting myeloid growth factors within 7 days of study entry, and a platelet count ≥50,000/µL, with patients required to be transfusion independent for at least 7 days, unless cytopenias are related to marrow metastasis as defined above. * With available haploidentical related donors.
Exclusion Criteria:
* Infectious disease: Active, uncontrolled infection or received a live vaccine within 30 days prior to study enrollment.
* Cardiac function: LVEF \<50% by echocardiogram, serious uncontrolled cardiac arrhythmias, or history of myocarditis or congestive heart failure (New York Heart Association Functional Classification III or IV)
* Pulmonary function: Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring systemic corticosteroid treatment.
* Renal function: Glomerular Function Rate (GFR) \<50 mL/min/1.73 m2 as measured by cystatin C or NM GFR
* Hepatic function: Total bilirubin \>5 mg/dL, AST and ALT \>10 times the upper limit of normal
* Concomitant medications: receiving \>0.5 mg/kg prednisone equivalent daily
* Receipt of any concomitant investigational treatments within 30 days at the time of the infusion of the IP. These investigational treatments include drugs, biologics, or devices that are still under investigation in clinical trials or research settings. The use of such agents may confound study results or pose additional safety risks
* Known allergy or hypersensitivity reaction to IL-2 injections
* Pregnant or breastfeeding women BIOLOGICAL: CIML-NK Cells
Neuroblastoma
Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant
Celeste Dourson - celeste.dourson@cchmc.org
ALL
PHASE2
NCT04230356
SCHEDULED ARM:
Inclusion Criteria:
* Recipient must be at least 21 days after stem cell infusion
* Clinical status must allow tapering of any steroids to \< 0.5mg/kg prednisone or other steroid equivalent
* No critical illness making VST infusion hazardous
Exclusion Criteria:
* Active acute GVHD grades II-IV.
* Uncontrolled relapse of malignancy.
* Infusion of ATG or alemtuzumab within 2 weeks prior to VST infusion. Alemtuzumab levels will be collected in the second week following stem cell infusion in patients who received alemtuzumab as part of their conditioning regimen. The level must be less than or equal to 0.15 prior to infusion of VSTs. In patients with level greater than 0.15, alemtuzumab levels can be checked serially until a level ≤ 0.15 is obtained. They would become eligible for scheduled VST infusion at that point.
TREATMENT ARM
Inclusion Criteria:
* Blood adenovirus PCR ≥1,000
* Blood CMV PCR ≥ 500
* Blood EBV PCR ≥ 9,000
* Plasma BKV PCR \>1,000
* Evidence of invasive adenovirus infection. Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from one site such as stool or blood or urine or nasopharynx. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture or PCR from more than 2 sites such as stool or blood or urine or nasopharynx.
* Evidence of invasive CMV infection, defined as pneumonitis, retinitis, colitis, hepatitis
* Evidence of EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation.
* Evidence of symptomatic BK virus infection, defined as hemorrhagic cystitis or BK nephropathy.
* No active acute GVHD grades II-IV
* No uncontrolled relapse of malignancy
* No infusion of ATG or alemtuzumab within 2 weeks of VST infusion.
* Clinical status must allow tapering of any steroids to \< 0.5mg/kg prednisone or other steroid equivalent BIOLOGICAL: Viral Specific T-cells (VSTs) Scheduled, BIOLOGICAL: Viral Specific T-cells (VSTs) Treatment
Allogeneic Stell Cell Transplant, Viral Infection
A Socio-ecological Approach for Improving Self-management in Adolescents With SCD (SC-Thrive)
Ama Wilson - ama.wilson@cchmc.org
ALL
13 years to 21 years old
NA
NCT06290401
Inclusion Criteria:
* Patient of a participating SCD Clinic
* Confirmed diagnosis of SCD
* 13-21 years of age
Exclusion Criteria:
* Another chronic disease (which would complicate measurement of patient activation)
* Non-English-speaking
* Cognitive or psychiatric disorder that the physician or study therapists believe would impair study participation. BEHAVIORAL: SCThrive, OTHER: SCHealthED
Anemia, Sickle Cell
adolescent and young adult (AYA), self-management, behavioral intervention, sickle cell disease
Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.
- cancer@cchmc.org
ALL
13 years and over
PHASE1
NCT04771572
Inclusion Criteria:
• Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below: -For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg.
• Eligible subject must have an advanced hematologic malignancy including: Group 1: Group 1a * Relapsed or refractory low risk tumor lysis CLL/SLL subjects (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm) who have received at least two prior therapies. Subjects may also have slowly progressed on irreversible BTK inhibitors while on treatment with these agents. * For CLL/SLL subjects who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows washout for 2 days as these subjects, progress quickly after treatment discontinuation and then remain eligible (steroids may be given during these two days to allow disease control). Group 1b * Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits; * Morphologically confirmed diagnosis of MDS/MPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits; * Chronic myelomonocytic leukemia (CMML) with \<9% blasts; * Or atypical chronic myeloid leukemia (aCML) with Hgb \> 10g/dL, WBC count \< 50 x 109 cells/L, \<10% immature circulating cells; * Or MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) with Hgb \> 10g/dL; * Or myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC) * CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and/or refractory to prior HMA therapy; * Relapsed and/or refractory MPN-BP as defined by WHO 2016 revised criteria that is transformed MPN with \>20% myeloid blasts in the peripheral blood or bone marrow, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits; * MDS subjects with refractory anemia with excess blasts (MDS-EB; subtype MDS-EB-1 or MDS-EB-2) as defined by WHO 2016 revised criteria and/or MDS with high- or very high-risk (risk score \> 4.5) per the Revised International Prognostic Scoring System (IPSS-R, refer to Appendix 11; Section 15.13) who have no available therapies known to provide clinical benefit; * Relapsed or refractory AML subjects (including de novo AML, secondary AML evolving from MDS or MPN or other antecedent hematologic disorder, and therapy-related AML) as defined by WHO 2016 revised criteria, subjects who have no available therapies known to provide clinical benefits; subjects with prior BCL-2 inhibitor therapy are permitted. WBC needs to be ≤ 25 × 109 cells/L at the time of initiating investigational therapy (hydroxyurea is allowed to control WBC prior to and during therapy). Group 1c * Relapsed or refractory low risk tumor lysis NHL (NHL histologies \[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\] are to be included per the 2016 World Health Organization \[WHO\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano; * Low risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate); * Low risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT; * Relapsed or refractory multiple myeloma (MM) subjects who have received a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 and have no treatment options available known to provide clinical benefit; * Low risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory; Group 1d * Relapsed or refractory ALL with dexamethasone run-in \[5 days, dexamethasone 10mg/m2 (divided BID)\]; * Or r/r ALL in remission but with detectable MRD (MRD +) by any detection method per institution standard of practice; * IT chemo (per institutional SOC) is permitted prior to LP-118 C1D1 dosing, and then concomitantly on treatment if in best interest of the subject; * Relapsed or refractory ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and/or tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and failed, or are currently ineligible/intolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and failed. * Relapsed or refractory ALL subjects with age between 13 - 18 years and have body weight ≥ 40kg, ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and/or tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and progressed, or are currently ineligible/intolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and progressed. Group 2 * Relapsed or refractory intermediate and high risk tumor lysis CLL/SLL subjects who have received at least two prior therapies; * Relapsed or refractory intermediate and high risk tumor lysis NHL (NHL histologies \[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\] are to be included per the 2016 World Health Organization \[WHO\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano; * Intermediate and high risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate); * Intermediate and high risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT; * Intermediate and high risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;
• For Group 1d ALL subjects only, white blood cell (WBC) count ≤ 25 × 109 cells/L at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).
• Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
• Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.
• Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows: Bone marrow criteria: * Group 1 (r/r low risk tumor lysis CLL/SLL (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm), NHL, RT, MM, T-PLL): * Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (An exception is for subjects with an ANC\<1 x 109/L and bone marrow heavily infiltrated with underlying disease) * Platelets ≥ 50 x 109/L on day of screening (entry platelet count must be independent of transfusion with 14 days of screening); * Hemostasis criteria: Activated partial thromboplastin time (APPT) and prothrombin time (PT) ≤ 1.5 × the upper limit of normal (ULN); * Renal function criteria: Serum creatinine ≤ ULN (per local institution reference range) or Calculated creatinine clearance (Cr Cl) ≥ 60 mL/min using 24-hour CrCl OR by Cockcroft-Gault formula using actual body weight. * Hepatic function criteria: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin \> 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).
• Females of childbearing potential (i.e., non-postmenopausal for at least 2 years or surgically sterile) and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 90 days after discontinuing study drug: * Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable; * Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy; * Intrauterine device; * Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) associated with inhibition of ovulation initiated for at least 1 month prior to study drug administration.
• Females of childbearing potential must have a negative pregnancy result as follows: * At Screening on a serum sample obtained within 7 days prior to the first study drug administration, and * Prior to dosing on a urine or serum sample obtained on the first day of study drug administration if ithas been \> 7 days since obtaining the serum pregnancy test results in Screening. * If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation
• Male subjects must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.
• Subject must be able to understand and voluntarily sign and date an informed consent form (ICF), approved by an IRB, prior to any protocol-related procedures.
Exclusion Criteria:
A subject will not be eligible for study participation if he/she meets any of the following criteria.
• Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is permitted.
• Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below. * Subject with breast cancer or prostate cancer on endocrine therapy with stable disease; * Continuation of maintenance therapy in patients with adequately treated malignancy * Adequately treated in situ carcinoma of the cervix uteri; * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. * Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment
• Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy): * Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \< 20 mg/day prednisone equivalent according to institutional guidelines to treat disease associated symptoms are permitted); * For MF subjects who come off JAK2 antagonists, allow washout for 2 days as these subject's progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease control). * Subjects in need of immediate cytoreduction should be excluded. * Any investigational therapy. * Live vaccines
• Subject has received the following medications, therapies, or natural products within 7 days prior to the first dose of LP-118: * Cytochrome P450, family 3, subfamily A (CYP3A) strong inhibitors (itraconazole, etc.), or substrates (Appendix 19); * Subject has received strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers within 14 days prior to the first dose of LP-118 (Appendix 19); * Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit; * There is a 28-day washout period required for subjects who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment, per discussion with the Medical Monitor.
• Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect his/her participation in this study. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the study, place the subject at unacceptable risk or interfere with the interpretation of the results. For subjects who have required surgical intervention for any above diseases within the past 6 months, a discussion with the Investigator and the Medical Monitor is needed.
• Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula \[QTcF = QT/RR (1/3)\])), a cardiovascular disability status of New York Heart Association Class ≥ 2 or associated other significant screening ECG or ultrasonic cardiogram abnormalities, per Investigator's judgement. For any subject with underlying RBBB or LBBB, cardiology review is needed to correct QTcF calculation using Sponsor recommended formula.
• Subject has significant a history of congenital long QT syndrome or Torsades de Pointes (TdP), uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke, or intracranial hemorrhage within 6 months prior to the first dose of LP-118.
• Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: * Uncontrolled active systemic infection (bacterial, fungal, viral); * Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HbsAg positive, or HbcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive); * Unexplained fever \> 38.5°C within 7 days prior to the first dose of study drug administration (at the discretion of the Investigator if the fever is considered attributed to the subject's malignancy or an explained infection may be enrolled).
• A female subject is pregnant or breast-feeding.
• Subject incapacity to swallow oral medications, with any malabsorption condition, known dysphagia, short-gut syndrome, gastroparesis, or other conditions that, in the opinion of the Investigator, may limit the ingestion or gastrointestinal absorption, distribution, metabolism and excretion of drugs administered orally.
• Subjects with known and active central nervous system (CNS) involvement at Screening.
• Subjects with known hypersensitivity to any of the components of LP-118 (see Investigators Brochure for a list of components).
• Subjects who are taking QT-prolonging drugs that are known to cause Torsades de Pointes (TdP) (See Appendix 17 for the list of medications that are associated with TdP). In the event a prohibited medication might cause TdP, the PI must first determine if the risk to benefit is in favor of the subject and then discuss with the Medical Monitor about that particular medication on a case-by-case basis.
• Major surgery within 14 days prior to the first dose of study drug.
DRUG: LP-118
Non Hodgkin Lymphoma, Richter Transformation, Multiple Myeloma, T-cell-prolymphocytic Leukemia, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myeodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Myelofibrosis, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Chronic Myelomonocytic Leukemia-2, Myelodysplastic Neoplasm in Blast Phase
Hematological Malignancies, Relapsed, Refractory
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
Milrinone for Prevention of Post-ligation Cardiac Syndrome Trial (MIDAS)
Traci Beiersdorfer - Traci.Beiersdorfer@cchmc.org
ALL
Up to 3 month(s) old
PHASE3
NCT06679855
Inclusion Criteria:
* Gestational age at birth ≤27 weeks (and 6 days) and postnatal age \< 3 months at intervention
* Invasive or non-invasive positive pressure respiratory support (does not include low flow nasal cannula)
* Hemodynamically significant PDA with minimum transductal diameter ≥1.0 mm within 2 days of intervention
* Decision by clinical team to proceed with PDA closure via surgical ligation or percutaneous cardiac catheterization based on clinical and echocardiography features of hemodynamic significance.
Exclusion Criteria:
* Any major congenital malformation
* Congenital heart disease (except small (≤1mm) muscular ventricular septal defects, or small/moderate (\<3mm) atrial septal defect)
* Acute renal failure defined by urine output \< 0.5 mL/kg/hour OR rise of serum creatinine by 0.3 mg/dL within 48 hours OR rise of serum creatinine more than 40% above baseline serum creatinine within prior 72 hours.
* Systemic administration of vasodilator/inodilator agents
* Prior history of arrhythmia DRUG: Milrinone infusion, DRUG: Placebo infusion
Post-ligation Cardiac Syndrome
Zemaira Eosinophilic Esophagitis Pilot Study (ZEEPS)
Regina Yearout - regina.yearout@cchmc.org
ALL
18 years to 70 years old
PHASE2
NCT05485155
Inclusion Criteria:
• Participant and/or legally authorized representative must be able to understand and provide informed consent prior to study procedures being performed.
• Willing and able to comply with study visits and activities
• Age ≥ 18 to ≤ 70 years at study enrollment
• Histologically active eosinophilic esophagitis (EoE) at time of screening or within 12 weeks prior to enrollment, with a peak count of ≥ 15 eosinophils (eos)/high powered field (hpf) in any region of the esophagus, with no other known cause for esophageal eosinophilia; involvement of eosinophilic inflammation in other gastrointestinal segments will be allowed but not required or sufficient.
• History of approximately 8 week standard of care (SOC) treatment (e.g., proton pump inhibitors (PPI's), topical corticosteroids) that did not adequately control or treat the EoE or documentation that such treatment was not tolerated. Participant may re-screen if this is not met.
• Stable medical management of EoE (and other eosinophilic disorders, if applicable) including stable dosage of medications in the 8 weeks prior to study enrollment, if applicable. Participants may be on baseline anti-EoE therapy (such as elimination diet, elemental diet, proton pump inhibitors (PPI), topical or systemic glucocorticoids (≤10 milligrams (mg) daily), immunosuppressive agents, cromolyn, and H1 and H2 anti-histamines) as long as there is agreement not to change their dosage.
• Willing to maintain current dietary regimen throughout the course of the study. Diet must have been stable for 8 weeks prior to baseline endoscopy.
Exclusion Criteria:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• Current active H. pylori infection. A history of H. pylori infection needs to have medical documentation of one of the three acceptable eradication tests: antigen, breath or histology. Participants with current active H. pylori infections can be re-screened for study participation in the future if they are treated and have medical documentation of one of the three acceptable eradication tests: antigen, breath or histology.
• Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome\*, Churg Strauss vasculitis, eosinophilic granuloma or a parasitic infection). \*Hypereosinophilic syndrome defined by multiple organ involvement (with the exception of atopic disease or eosinophilic gastrointestinal disorder (EGID)) and persistent blood absolute eosinophil count ≥1500/microliter.
• Systemic gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease not including chronic gastritis, chronic duodenitis, mucosal eosinophilia or other EGID's.
• Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
• Known immunoglobulin A (IgA) deficiency (i.e., IgA level \< 8 mg/dL at screening).
• Current coronavirus disease of 2019 (COVID-19) infection (i.e., detection of the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before the screening endoscopy using testing done at the clinical site).
• Hematological disorders that prevent the blood from clotting (e.g., hemophilia, Von Willebrand disease, clotting factor deficiencies).
• Currently on anti-coagulation medications (except aspirin/Non-steroidal anti-inflammatory drugs).
• Known history of hypersensitivity following infusions of human blood or blood components (e.g., human immunoglobulins or human albumin).
• Known history of hypersensitivity or anaphylaxis to Zemaira or other A1AT products.
• Uncontrolled, or poorly controlled, comorbid conditions including, but not limited to, cardiovascular diseases, hypertension and diabetes as defined by the following criteria: * A myocardial infarction within the last 6 months. * Blood pressure \> 179/99 mmHg * Diabetics with a hemoglobin A1C (HbA1C) \> 7% and that are deemed to have uncontrolled diabetes as defined by the physician
• History of cancer: Individuals who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained. Individuals who have had other malignancies are eligible provided that the individual is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• Current or recent use of any investigational drug (within 3 months or 5 half-lives, whichever is longer, prior to screening).
• Currently participating or planning to participate in another clinical study involving an investigational drug during the course of this study.
• Presence of steroid-responsive diseases (e.g., asthma) with a recent (within the last 6 months) history of disease exacerbations requiring steroid treatment.
• Current use of systemic steroids with daily dose \> 10 mg for any reason or steroid burst for \> 3 days within 1 month of screening.
• Current pregnancy or breastfeeding.
• Any esophageal stricture unable to be passed with a standard, diagnostic upper endoscope.
• Esophageal varices or interventional treatment for esophageal varices that, in the opinion of the investigator, would put the participant at undue risk for significant complications from an endoscopy procedure.
• History of alcohol or drug abuse within 6 months prior to screening.
• Participant or his/her immediate family is a member of the investigational team.
• Presence of clinically significant laboratory abnormalities at the screening that meets one or more of the following criteria:
• Serum alanine aminotransferase (ALT) ≥ 3 times upper limit of normal (ULN)
• Serum total bilirubin ≥2 times ULN
• Absolute neutrophil count (ANC) ≤ 1000 cells/mm3
• Hemoglobin (Hgb) ≤ 10.0 g/dL
• Platelet count ≤ 100,000/mm3
• Glomerular Filtration Rate (GFR) ≤ 44 mL/min/1.73 m2
• Planned or anticipated major surgical procedure during the study.
• Known or suspected immunodeficiency disorder, including human immunodeficiency disorder (HIV) or a history of invasive opportunistic infections (e.g., tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis, or an infectious etiology of esophagitis (e.g. cytomegalovirus or Candida) despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged infections suggesting an immune-compromised status as judged by the investigator.
• Planned or anticipated use of any prohibited medications and procedures during the study.
• Currently on Zemaira for other indications.
• Initiation, discontinuation or change in the dosage regimen of the following medications within 8 weeks prior to the baseline endoscopy: Proton pump inhibitors Leukotriene inhibitors Nasal and/or inhaled corticosteroids Participants on a stable dose of these medications for at least 8 weeks prior to the baseline endoscopy may be included in the study. PPI and leukotriene inhibitor dosing must not change during the study, but nasal and/or inhaled corticosteroids can be increased if there is a deterioration in the condition for which the medications are prescribed.
• Presence of the following esophageal disorders: achalasia cardia, Barrett's esophagus or precancerous lesions noted on the endoscopy.
• Women of childbearing potential, or male participants with female partners of childbearing potential, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 12 weeks after the last dose. Highly effective contraceptive measures include:
• Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) for one month prior to screening
• Intrauterine device; intrauterine hormone-releasing system
• Bilateral tubal ligation
• Vasectomized partner
• And/or sexual abstinence
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
DRUG: Alpha-proteinase inhibitor
Eosinophilic Esophagitis
I-InTERACT Preterm Parenting (I2P-RCT)
Zyah Flagg - zyah.flagg@cchmc.org
ALL
3 years to 8 years old
NA
NCT06767293
Inclusion Criteria:
* Born at \< 32 weeks gestational age.
* Total T score of \> 55 on the Child Behavior Checklist Total or Externalizing Behavior Scales OR Total T score of \> 55 on the Eyberg Child Behavior Inventory total problem- or total intensity-scale.
* English is the primary spoken language in the home.
Exclusion Criteria:
* Is not 18 years or older.
* Participant will be excluded from the study if the child does not reside with the caregiver at least half-time; the caregiving situation is not stable (i.e., there must be no scheduled custody hearings).
* English is not the primary language spoken in the home.
* Caregivers with a psychiatric hospitalization in the past year. BEHAVIORAL: I-InTERACT Parenting Intervention (I2P) and coaching sessions, BEHAVIORAL: I-InTERACT Parenting Microlearning Intervention (I2P Micro) and coaching sessions, OTHER: Internet Resources
Child Behavior Problem, Preterm, Parent-Child Relations, Parenting
telehealth, online learning, microlearning
Dichoptic Treatment for Amblyopia in Children 4 to 7 Years of Age (ATS23)
Jillian Bulman - jillian.bulman@cchmc.org
ALL
4 years to 7 years old
PHASE3
NCT06380517
At the time of enrollment, individuals must meet all the following inclusion criteria to be eligible to participate in the study.
• Age 4 to 7 years.
• Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) using the ATS-HOTV VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
• VA in the amblyopic eye 20/40 to 20/200 inclusive.
• Age-normal VA in the fellow eye:44,45 • 4 years: 20/40 or better; 5-6 years: 20/32 or better; 7 years: 20/25 or better
• Interocular difference ≥ 3 logMAR lines (i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA).
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated).
• Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be \<=5 prism diopters (∆) by SPCT at distance and near fixation (see #7 below). * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia).
• Criteria for anisometropia: At least one of the following criteria must be met: * ≥1.00 D difference between eyes in spherical equivalent (SE). * ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• Criteria for combined-mechanism: Both of the following criteria must be met: * A criterion for strabismus is met (see above). * ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• No more than 2 weeks (cumulative) of prior dichoptic treatment.
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months: * Hypermetropia of 2.50 D or more by SE * Myopia of amblyopic eye of 0.50D or more SE * Astigmatism of 1.00D or more * Anisometropia of more than 0.50D SE NOTE: Monocular or binocular contact lens wear is allowed provided the contact lenses meet the refractive error correction requirements below. For each child, all testing must be performed using the same form of optical correction (i.e., no changing between contacts and spectacles).
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months: * SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes). * SE must not be under corrected by more than 1.50D SE. * Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism. * Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is \>1.00D. * Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn: * For at least 18 weeks OR until VA stability is documented (defined as \<0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 9 weeks apart). * For determining VA stability (non-improvement): * The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed), * The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks. * NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
• Participant is willing to wear the Luminopia headset.
• Participant is willing to continue full-time spectacles/contact lens wear (if needed).
• Participant is willing to accept assignment to either dichoptic shows (view 1 hour per day 6 days per week) OR part-time patching (2 hours per day 7 days per week) for 26 weeks.
• Interpupillary distance of 52mm to 72mm inclusive.
• Investigator is willing to prescribe Luminopia or patching per protocol.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center.
• Relocation outside area of active PEDIG site within the next 52 weeks is not anticipated. Individuals meeting any of the following criteria will be excluded from study participation.
• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment.
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment).
• Myopia greater than -6.00D spherical equivalent in either eye.
• Previous intraocular or refractive surgery.
• Known skin reactions to patch or bandage adhesives.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted).
• Diplopia more than once per week over the last week prior to enrollment by parental report.
• History of light-induced seizures.
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Participation in a prior study involving patching for amblyopia
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.
• Age 4 to 7 years.
• Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) using the ATS-HOTV VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
• VA in the amblyopic eye 20/40 to 20/200 inclusive.
• Age-normal VA in the fellow eye:44,45 • 4 years: 20/40 or better; 5-6 years: 20/32 or better; 7 years: 20/25 or better
• Interocular difference ≥ 3 logMAR lines (i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA).
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated).
• Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be \<=5 prism diopters (∆) by SPCT at distance and near fixation (see #7 below). * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia).
• Criteria for anisometropia: At least one of the following criteria must be met: * ≥1.00 D difference between eyes in spherical equivalent (SE). * ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• Criteria for combined-mechanism: Both of the following criteria must be met: * A criterion for strabismus is met (see above). * ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• No more than 2 weeks (cumulative) of prior dichoptic treatment.
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months: * Hypermetropia of 2.50 D or more by SE * Myopia of amblyopic eye of 0.50D or more SE * Astigmatism of 1.00D or more * Anisometropia of more than 0.50D SE NOTE: Monocular or binocular contact lens wear is allowed provided the contact lenses meet the refractive error correction requirements below. For each child, all testing must be performed using the same form of optical correction (i.e., no changing between contacts and spectacles).
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months: * SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes). * SE must not be under corrected by more than 1.50D SE. * Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism. * Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is \>1.00D. * Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn: * For at least 18 weeks OR until VA stability is documented (defined as \<0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 9 weeks apart). * For determining VA stability (non-improvement): * The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed), * The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks. * NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
• Participant is willing to wear the Luminopia headset.
• Participant is willing to continue full-time spectacles/contact lens wear (if needed).
• Participant is willing to accept assignment to either dichoptic shows (view 1 hour per day 6 days per week) OR part-time patching (2 hours per day 7 days per week) for 26 weeks.
• Interpupillary distance of 52mm to 72mm inclusive.
• Investigator is willing to prescribe Luminopia or patching per protocol.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center.
• Relocation outside area of active PEDIG site within the next 52 weeks is not anticipated. Individuals meeting any of the following criteria will be excluded from study participation.
• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment.
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment).
• Myopia greater than -6.00D spherical equivalent in either eye.
• Previous intraocular or refractive surgery.
• Known skin reactions to patch or bandage adhesives.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted).
• Diplopia more than once per week over the last week prior to enrollment by parental report.
• History of light-induced seizures.
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Participation in a prior study involving patching for amblyopia
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.
DEVICE: Luminopia, OTHER: Eye Patch
Amblyopia
Dichoptic, Luminopia, Patching, movie
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
Observational Study of THC Concentrations in Acute Cannabis-induced CNS Depression
Allison Ackermann - allison.ackermann@cchmc.org
ALL
NCT06017622
Inclusion Criteria:
•
Inclusion Criteria:
The patient is younger than 18 years old.
• The patient visits the ED with signs and symptoms of suspected acute cannabis-induced CNS depression, as evidenced by the patient suffering from clinically significant CNS depression combined with the following criteria: a) Exposure to cannabis or cannabis-derived products, or other products containing any CB1 agonist (such as Δ8-THC, HHC) within the last 12 hours, confirmed through one or more of the following: i. Positive toxicology testing, or ii. Other clinical evidence, such as reliable collateral history (e.g., from caregivers, EMS personnel, or witnesses), physical evidence (e.g., product packaging), or a consistent self-report. AND EITHER b) Symptoms are associated with cannabis exposure and developed during, or shortly after, cannabis exposure; OR c) In the judgment of investigator or designated clinician, the presentation includes symptoms consistent with acute cannabis-induced CNS depression (e.g. respiratory rate depression, increased sedative effects).
• Blood samples are taken as part of routine clinical procedures, or the patient has an IV line through which blood can be taken.
• The LAR is willing and able to provide consent.
• The patient is willing and able to provide assent, if applicable and feasible, based on age and clinical condition. Exclusion criteria A potential patient who meets any of the following criteria will be excluded from participation in this study:
• Anything that, in the opinion of the PI, would place the patient at increased risk or preclude the patient's compliance with or completion of the study.
• Patient is presenting with signs or symptoms that are better explained by another medical condition or mental disorder, exposure to a drug other than cannabis, and, at the PI's discretion, are not induced by acute cannabis exposure.
• Patient presenting with cannabis use disorder (CUD), cannabis hyperemesis syndrome (CHS) or cannabis withdrawal syndrome (CWS)
• Patients who are brought in by law enforcement, i.e., cannabis intoxication associated with a vehicle accident (driving under the influence).
Acute Cannabis-induced CNS Depression
TSC Biosample Repository and Natural History Database
Salma Ihiri - salma.ihiri@cchmc.org
ALL
NCT05676099
Inclusion Criteria:
* Diagnosis of tuberous sclerosis complex or lymphangioleiomyomatosis (sporadic LAM).
Exclusion Criteria:
\- PROCEDURE: Phlebotomy, PROCEDURE: Buccal (cheek) swab, GENETIC: Genetic Testing, OTHER: Tissue donation after routine clinical procedure
Tuberous Sclerosis, Lymphangioleiomyomatosis
A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT (ENOVIA)
Brady Landon - brady.landon@cchmc.org
ALL
2 month(s) and over
PHASE3
NCT07387367
Inclusion Criteria:
• Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
• Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
• In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
• Has adenoviremia, based on any of: * AdV viremia DNA ≥10,000 IU/mL, OR * Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR * AdV viremia DNA of ≥1,000 IU/mL, AND 1\. Lymphocyte count \<180/mm3, OR 2. Received T cell depletion, cord blood, or haploidentical transplant, OR 3. prior alemtuzumab, OR 4. anti-thymocyte globulin (ATG)
Exclusion Criteria:
• Subject received an allo-HCT with a matched sibling donor
• Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
• Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
• Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
• Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
DRUG: cidofovir, DRUG: Brincidofovir
Adenovirus Infections
Brincidofovir, Cidofovir, Adenovirus, allo-HCT, BCV-PA02, ENOVIA
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
2 days to 17 years old
NA
NCT05376267
Inclusion criteria:
* Age 2 days to \< 18 years with corrected gestational age of at least 38 weeks
* Chest compressions for at least 2 minutes
* Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
* Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
* Definitive temperature control device initiated
* Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
* Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours
Exclusion criteria:
* Glasgow Coma Motor Score (GCMS) = 6
* LAR does not speak English or Spanish
* Duration of Cardiopulmonary Resuscitation (CPR) \> 60 minutes
* Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
* Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
* Pre-existing terminal illness, unlikely to survive to one year
* Cardiac arrest associated with brain, thoracic, or abdominal trauma
* Active and refractory severe bleeding prior to randomization
* Extensive burns or skin lesions incompatible with surface cooling
* Planned early withdrawal of life support before 120 hours
* Sickle cell anemia
* Pre-existing cryoglobulinemia
* Non-fatal drowning in ice covered water
* Central nervous system tumor with ongoing chemotherapy
* Previous enrollment in P-ICECAP trial
* Prisoner
* Chronic hypothermia
* New post-cardiac arrest diabetes insipidus
* Pregnancy
DEVICE: Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
- cancer@cchmc.org
ALL
PHASE3
NCT03067181
Inclusion Criteria:
* There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT \[all sites\])
* Standard risk 1: Patients must be \< 11 years of age at enrollment
* Standard risk 2: Patients must be \>= 11 and \< 25 years of age at enrollment
* Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with malignant germ cell tumor (stage II or higher).
* Histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment , with the following exceptions:
* Among patients were initially diagnosed with completely resected non-seminoma malignant GCT and later recur during observation post surgery, a diagnostic biopsy is not required for enrollment if elevated tumor markers rise to \> 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart. The pathology report of initial surgery should be provided
* Patients may be enrolled without histologic or cytologic confirmation in the rare case where there are exceptionally raised tumor markers (alpha fetoprotein \[AFP- ≥ 500 ng/mL or HCG ≥ 500 IU/L) and radiologic features consistent with GCT. In addition, the treating clinician must deem that the patient's tumor is not suitable for upfront resection and that a biopsy is not in the patient's best interest; or that there is a need to start therapy urgently
* Low risk immature teratoma (IT); site: ovarian; stage: any; grade: any; histology: pure immature teratoma, mixed immature and mature teratoma, (may contain microscopic foci of yolk sac tumor \[\< 3 mm\], but no other pathological evidence of MGCT); tumor markers: alpha-FP =\< 1,000 ng/mL, beta-HCG institutional normal; all ages
* Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
* Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain only seminoma; may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
* Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC-IV, (International Germ Cell Consensus Classification \[IGCCC\] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \< 11
* Standard risk 2 (SR2)
* Site: ovarian; stage: COG stage II, III, and III-X, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma: must be IGCCC good risk; post op: alpha-FP \< 1,000 ng/mL, beta-HCG \< 5,000 IU/mL and lactate dehydrogenase (LDH) \< 3.0 x normal; age (years) \>= 11 and \< 25
* Notes:
* IGCCC criteria only apply to SR2 patients with a testicular primary tumor
* Use post-op tumor marker levels to determine IGCCC risk group
* Pure seminoma patients are not eligible for the standard risk arms of the study
* For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
* Adequate renal function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A serum creatinine based on age/sex as follows (within 7 days prior to enrollment): (mg/dL)
* 1 month to \< 6 months male: 0.4 female: 0.4
* 6 months to \< 1 year male: 0.5 female: 0.5
* 1 to \< 2 years male: 0.6 female: 0.6
* 2 to \< 6 years male: 0.8 female: 0.8
* 6 to \< 10 years male: 1 female: 1
* 10 to \< 13 years male: 1.2 female: 1.2
* 13 to \< 16 years: male: 1.5 female: 1.4
* \>= 16 years male: 1.7 female: 1.4
* Total bilirubin =\< 2 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3 (within 7 days prior to enrollment) AND
* Platelet count \>= 75,000/mm\^3 (within 7 days prior to enrollment)
* Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
* Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes \[PROs\] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
* \>= 11 and \< 25 years old at enrollment
* Able to fluently speak and read English
* Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
* Followed for cancer or survivorship care at one of the following institutions:
* Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
* Dana Farber/Harvard Cancer Center
* Hospital for Sick Children
* Children's Hospital of Eastern Ontario
* Oregon Health and Science University
* Seattle Children's Hospital
* Yale University
Exclusion Criteria:
* Patients with any diagnoses not listed including:
* Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
* Pure ovarian or extragonadal dysgerminoma/seminoma
* Pure mature teratoma
* Pure immature teratoma with alpha-fetoprotein (AFP) \>= 1000 ng/mL
* "Poor risk" GCT (age \>= 11 years old and COG stage IV ovarian, COG stage II- IV extragonadal, or IGCCC intermediate or poor risk testicular), or
* Primary central nervous system (CNS) germ cell tumor
* Germ cell tumor with somatic malignant transformation
* Spermatocytic seminoma
* Patients must have had no prior systemic therapy for the current cancer diagnosis
* Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain \[stage IV disease\] would be considered poor risk and therefore not eligible for this trial)
* Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\]) OTHER: Best Practice, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Bleomycin Sulfate, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Pulmonary Function Test, OTHER: Questionnaire Administration
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
Proton and Photon Consortium Registry (PPCR): A Multi Center Registry of Pediatric Patients Treated With Radiation Therapy
- cancer@cchmc.org
ALL
Up to 21 years old
NCT01696721
Eligibility Criteria:
• Patients treated with radiation therapy at one of the participating centers
• Age \< 22 at time of treatment start.
• Patients may be enrolled regardless of previous local or systemic treatments received prior to enrollment in the PPCR.
• Patients may be enrolled regardless of other current local or systemic treatments or disease extent.
• Patients may be enrolled on the PPCR concurrently with another study or clinical trial.
• Patients treated with radiation therapy at one of the participating centers
• Age \< 22 at time of treatment start.
• Patients may be enrolled regardless of previous local or systemic treatments received prior to enrollment in the PPCR.
• Patients may be enrolled regardless of other current local or systemic treatments or disease extent.
• Patients may be enrolled on the PPCR concurrently with another study or clinical trial.
OTHER: No intervention
Pediatric Patients Treated With Radiation Therapy
Proton Therapy, Pediatrics, Radiation Oncology, Photon Therapy
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
Shwachman Diamond Syndrome Registry and Study (SDSR)
Caitlin Cottrell - caitlin.cottrell@cchmc.org
ALL
NCT06056908
Inclusion Criteria:
Shwachman Diamond syndrome, Shwachman-Diamond Syndrome-Like conditions, or a genetically undefined condition that shares clinical features with Shwachman Diamond Syndrome.
* Biallelic mutations in SBDS, or pathogenic mutations in DNAJC21, EFL1, or SRP54 OR
* Shwachman-Diamond Syndrome defined clinically OR
* Clinically suspected Shwachman-Diamond Syndrome OR
* Phenotypic features suggestive of SDS OR
* Parents, siblings, and other blood relatives of any age, living and deceased, of patients with SDS or SDS-Like conditions are eligible for this study
Exclusion Criteria:
• Patients with other diagnosed causes of bone marrow failure, exocrine pancreatic insufficiency and cancer predisposition will be excluded. Shwachman-Diamond Syndrome, Shwachman-Diamond Syndrome-Like
Bone marrow failure, Inherited bone marrow failure syndromes, Bone marrow, Neutropenia, Leukemia, MDS, Pancreas, Cancer predisposition
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
Down Syndrome Obstructive Sleep Apnea (DOSA)
Suzanna Hicks - suzanna.hicks@cchmc.org
ALL
5 years to 18 years old
PHASE2
NCT06043440
Inclusion Criteria:
• Ages 5.0 to 17.9 years at the time of screening
• Children with OSA and obstructive apnea hypopnea index (OAHI) ≥5/hour.
• Absence of clinically significant hypoxia defined as oxygen saturation \<88% for 5 minutes or episodic desaturation to 60% as these levels would otherwise identify children eligible to routinely receive oxygen.
• Favorable response to oxygen therapy (allowing randomization) will be defined as follows:
• Oxygen saturation nadir \>92% and
• Decrease in obstructive index \< 5 / hour or by \> 50% from screening PSG
• Reaching an optimum oxygen flow which is defined as the flow that achieves the lowest level of AHI with maximum CO2 level less than 65 mmHg observed for 5 consecutive minutes and or an increase in CO2 by less than 15 points above baseline. The above criteria are observed while the patient spends a minimal of 30 minutes in the supine position and at least one cycle of rapid eye movement (REM) sleep.
• Oxygen flow required does not exceed 3.0 LPM and does not exceed a FiO2 \> 40 %.
• Willingness to comply with all study procedures and available for duration of study.
• At baseline the participant attempts to perform the neuropsychological tests
Exclusion Criteria:
• Current CPAP use with documented compliance(\> 4 hrs/ night; \> 70% of nights).
• Oxygen saturation \< 90% at rest during wakefulness.
• Chronic daytime or nighttime use of supplemental oxygen.
• Smoker in the child's bedroom.
• Unrepaired congenital heart disease.
• Moderate to severe pulmonary hypertension requiring treatment with oxygen and or pulmonary vasodilator.
• Unable to participate in a PSG.
• Individuals who develop alveolar hypoventilation with oxygen as previously defined.
• Other severe chronic diseases determined by their provider as making them poor study candidates.
• Enrolled or planning to enroll in another study that may conflict with protocol requirements or confound results in this trial.
• Documented clinically significant untreated hypothyroidism
• Children with adenotonsillar hypertrophy who are candidates for adenotonsillectomy and parents agree to the surgery.
DRUG: Oxygen
Down Syndrome, Obstructive Sleep Apnea
Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials (Nof1)
Sharon Kadon - sharon.kadon@cchmc.org
ALL
6 years and over
NA
NCT04580368
Inclusion Criteria:
* Signed informed consent (and assent when applicable)
* Willing and able to adhere to the study visit schedule and protocol requirements
* Male or Female ≥6 years old and within the FDA-approved range for the proposed modulator drug
* Ivacaftor: ≥4 months old
* Lumacaftor/Ivacaftor: 2 years old
* Tezacaftor/Ivacaftor: 12 years old
* Elexacaftor/Tezacaftor/Ivacaftor: ≥12 years old
* At least one rare CFTR variant (incidence of \<5% of the CF population)
* Documentation of a CF diagnosis as evidenced by one or more clinical features of CF plus at least one of the following:
* Sweat Chloride ≥60mmol/L by quantitative pilocarpine iontophoresis
* Two mutations in the CFTR gene
* Abnormal nasal potential difference (NPD) testing supportive of a CF diagnosis
* FEV1 \> 50% predicted for age
* Stable chronic CF therapies with no changes in \>28 days (except for chronic cycled inhaled antibiotics such as tobramycin)
* Prescribed CFTR modulator by a licensed physician
* No contraindication to treatment with the selected drug at the time of treatment initiation
Exclusion Criteria:
* Presence of any condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient and/or quality of the data
* For women of child bearing potential:
* Positive pregnancy test or known pregnancy at Visit 1
* Lactating
* Unwilling to practice a medically acceptable form of contraception (acceptable forms include abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study
* BMI \< 10th percentile for age (if \<18 years old) or \< 20kg/m2 (if ≥18 years old)
* FEV1 ≤ 50% predicted for age
* Growth of CF pathogens from sputum cultures that are associated with unstable disease (e.g., nontuberculous mycobacteria, Burkholderia spp) within six months of enrollment
* Concomitant use of CYP3A inducers or inhibitors (e.g., voriconazole, fluconazole, rifampin) or prednisone (\>20mg daily)
* Concomitant conditions:
* Poorly controlled diabetes mellitus (HbA1c \>8.5 or glucosuria as noted below)
* Advanced CF liver disease (cirrhosis with portal hypertension, ascites, or abnormal liver laboratory testing as noted below)
* End stage renal disease
* History of organ transplantation
* Additional medical conditions that in the opinion of the Investigator place the patient at risk of participation or may impact the patient's ability to complete the trial (e.g., uncontrolled depression, anxiety disorder, poor adherence to CF therapies, active ABPA)
* Any of the following abnormal laboratory values at the Screening Visit:
* CBC
* WBC \>15,000 K/mcL or ANC \<1,500 K/mcL
* Hemoglobin \<10 gm/dL
* Platelets \<50,000 K/mcL
* Chemistries
* \>2+ Glucosuria
* Clinically significant abnormalities as assessed by the Investigator
* Glomerular filtration rate ≤50 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)
* Hepatic Function Testing / Coagulation Testing
* ≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
* ≥3 × ULN alanine aminotransferase (ALT)
* ≥3 × ULN gamma-glutamyl transpeptidase
* Total or direct bilirubin \>2 × ULN
* INR \> 1.5 x ULN
* Positive pregnancy test DRUG: CFTR Modulators
Cystic Fibrosis
CFTR modulators, cystic fibrosis, HNE, human nasal epithelial cells, NPD, nasal potential difference, air-liquid interface, N-of-1
Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome (DiNO)
Abigayle Gibson - Abigayle.Gibson@cchmc.org
ALL
0 years to 21 years old
NCT06690801
Inclusion Criteria:
* Age \>37 weeks corrected gestational age to 21 years, including adults lacking the capacity to consent.
* Within 72 hours of the start of invasive mechanical ventilation and meet the criteria for pediatric ARDS (new infiltrate on chest imaging and a known ARDS risk factor within 7 days of the onset of hypoxemia) and either meet criteria for moderate or severe pediatric ARDS between 4-72 hours of IMV (OI ≥ 8 or OSI ≥ 7.5) OR have an OI ≥ 20 or an OSI ≥ 14 x 15 minutes between 0-4 hours of IMV.
* Subgroup of children eligible for longituduinal Blood Collection: Children with severe PARDS (OI ≥ 16 or an OSI ≥ 12 between 4-72 hours of IMV) or those with an OI ≥ 20 or an OSI ≥ 14 for 15 minutes between 0-4 hours of IMV will be eligible for collection of longitudinal plasma samples.
Exclusion Criteria:
* Non-conventional invasive mechanical ventilation (i.e. High Frequency Oscillatory Ventilation, Airway Pressure Release Ventilation) at the time of ICU admission
* ECMO or iNO (or other inhaled pulmonary vasodilator therapy) at the time of ICU admission
* Significant lower airways obstruction (examination of ventilator and capnography waveforms by site study or medical team)
* Air leak \>20% (endotracheal tube, tracheostomy tube, or thoracostomy tube)
* Home Invasive Mechanical Ventilation
* Cyanotic Congenital Heart Disease
* Previous enrollment in the DiNO study
* Do not resuscitate order at the time of pediatric ARDS diagnosis.
* Blood gas not obtained prior to initiation of ECMO, iNO, or non-conventional ventilation. Acute Respiratory Distress Syndrome
Pediatrics, Mechanical Ventilation, Inhaled Nitric Oxide
Primary Sclerosing Cholangitis in Children
Erin Chapman - erin.chapman@cchmc.org
ALL
2 years to 25 years old
NCT04181138
Inclusion Criteria:
Patients with the clinical diagnosis of large or small duct PSC made at any time prior to enrollment are screened for eligibility to participate in this prospective cohort study. The site PI will determine eligibility following review of MRCP or ERCP images with the site radiologist to confirm presence of an abnormal cholangiogram at the time of diagnosis of large duct PSC. Liver histopathology obtained at the time of diagnosis of small duct PSC will be reviewed with the site pathologist prior to enrollment.
Individuals must meet all of the Inclusion criteria in order to be eligible to participate in the study:
• Aged 2 through 25 years at time of screening.
• Diagnosis of large duct PSC based on review of cholangiogram by MRC, ERC, or intraoperative cholangiogram (IOC) by the site radiologist and interpreted to be consistent with PSC, based on one or more of the following: * Focal structuring of the bile duct(s) * Dominant stricture of the common bile duct * Saccular dilatation of bile duct(s) * Beaded appearance of bile duct(s) * Pruning appearance of the distal bile duct branches AND/OR
• Diagnosis of small duct PSC based on review of liver histopathology by the site pathologist and interpreted to be compatible with PSC: * Probable small duct PSC: biopsy with ≥3 of 5 criteria: periductal edema, concentric inflammation, bile duct injury, ductular reaction, and neutrophils in bile ducts (cholangitis) OR... * Definitive small duct PSC: Periductal fibrosis/ "onion skinning" around interlobular bile ducts or smaller profiles
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Able to provide informed consent/assent Participants for the imaging study are eligible if they are:
• Aged 8 through 25 years at the time of screening
• No absolute contraindication to MRI
• No skin condition that could be aggravated by MREL
• Meet all other eligibility criteria of the PSC Observational Study
• For whom none of the exclusion criteria apply
Exclusion Criteria:
An individual who meets any of the following criteria at baseline will be excluded from participation in this study.
• History of liver transplantation
• History bone marrow transplantation
• History of primary or acquired immunodeficiency predisposing to secondary sclerosing cholangitis, for instance: hyper-IgM syndrome, severe combined immunodeficiency (SCID) syndrome, common variable immunodeficiency (CVID) syndrome, cartilage hair hypoplasia syndrome, or HIV/AIDS
• History of histiocytosis, including Langerhans cell histiocytosis (LCH), or hemophagocytic lymphohistiocytosis (HLH)
• History of ischemic cholangitis
• History of portal vein thrombosis with biliopathy, veno-occlusive disease, or abdominal radiation vasculopathy
• History of recurrent pyogenic cholangitis
• History of biliary tract surgery for cholecystolithiasis prior to cholangiogram/liver biopsy evaluated to determine enrollment
• History of biliary tract surgery for choledochal cyst
• History of hepatocellular carcinoma, or hepatoblastoma
• History of surgical biliary trauma
• History of congenital cytomegalovirus (CMV) hepatitis
• History of Sickle Cell Disease
• History of cystic fibrosis, biliary atresia, Caroli disease/congenital hepatic fibrosis, or progressive familial intrahepatic cholestasis type 3/MDR3 disease
• History of cardiac hepatopathy.
• History of metabolic disorders, including Wilson's disease, glycogen storage disorder, Alpha-1 Antitrypsin deficiency
• Diagnosis of systemic lupus erythematosus (SLE)
• Concurrent pregnancy at the time of enrollment -
Primary Sclerosing Cholangitis, Liver Diseases, Cholangitis, Sclerosing
Pediatric Liver Disease, Primary Sclerosing Cholangitis
A Phase 3 Study of Revaccination in Subsequent Pregnancies With Bivalent RSV Vaccine and Duration of Protection of a Single Dose
Benjamin Kercsmar - Benjamin.Kercsmar@cchmc.org
ALL
Not specified
PHASE3
NCT06866405
Pregnant Participants-Cohort 1 and Cohort 2 Key Inclusion Criteria
* Women aged 18 to 49 who are pregnant, between 24 and 36 weeks along, and expecting one baby without known risks for complications can participate.
* Had the RSVpreF or Abrysvo vaccine during a previous pregnancy.
* Had an ultrasound scan at 18 weeks or later during their current pregnancy, with no major fetal problems detected.
* Based on their medical history, physical check-up, and the doctor's judgment, they are found suitable to join the study.
* Agrees to let their baby take part in the study and gives their permission.
* Able to sign a consent form, agreeing to follow the rules and conditions of the study.
Key Exclusion Criteria
* Received any approved or experimental RSV vaccine since their previous pregnancy.
* Has a pre-pregnancy body mass index (BMI) over 40 kg/m2.
* History of a severe bad reaction to a vaccine or a serious allergic reaction (like anaphylaxis) to any ingredient in the study vaccine or a similar vaccine.
* Current pregnancy problems or issues at the time of giving consent.
* Previous pregnancy issues or problems at the time of giving consent.
* Women who are breastfeeding at the time of enrollment
Infant Participants
* Proof that the parent(s) or legal guardian(s) has signed and dated a consent form.
* Parent(s) or legal guardian(s) must agree to attend scheduled visits and follow the study plan, including laboratory tests and other procedures.
Nonpregnant Participants-Cohort 3 Key Inclusion Criteria
* Have already received one dose of the RSVpreF vaccine during their previous pregnancy as part of the Pfizer clinical trial, and the results from that time can be used for this study.
* Able to sign a consent form, agreeing to follow the rules and requirements of the study.
Key Exclusion Criteria
* Received any approved or experimental RSV vaccine after participating in the Pfizer clinical trial.
* Taking part in other studies with new drugs within 28 days before giving consent or during the study period.
BIOLOGICAL: RSVpreF, BIOLOGICAL: Placebo
RSV Infection
Pregnancy, RSV vaccine, RSV, Maternal immunization
Impact of Soymilk on Liver Disease Severity of Children With Non-alcoholic Fatty Liver Disease (NAFLD)
Ann Popelar - Ann.Popelar@cchmc.org
ALL
5 years to 16 years old
PHASE2
NCT06133101
Inclusion Criteria:
* Children with overweight/obesity
* Known NAFLD or elevated ALT (\>30)
Exclusion Criteria:
* Baseline habitual (\>3 days per week) consumption of soy foods
* Allergy to soy or cow's milk protein
* Inability to undergo MRI
* Recent (past 8 weeks) antibiotic exposure
* Treatment for existing endocrine disorders
* MRI PDFF \<10% DRUG: Standard Soy Milk, DRUG: 2% Fat Cow's Milk
Non-Alcoholic Fatty Liver Disease
NAFLD
MRI Biomarkers in as Predictor of Clinical Endpoints in Pediatric Autoimmune Liver Disease
Alexander Miethke, MD - alexander.miethke@cchmc.org
ALL
6 years to 23 years old
NCT03178630
Inclusion Criteria:
• Age 6-23 years old.
• Established clinical diagnosis of AIH or PSC.
Exclusion Criteria:
• History of liver transplantation.
• Chronic Hepatitis B or untreated hepatitis C virus infection.
• Pregnancy.
• Absolute contraindication for MRI (e.g. pacemaker, metallic implants, claustrophobia).
• Diagnosis of cystic fibrosis or biliary atresia
• Diagnosis of cardiac hepatopathy.
• Diagnosis of Wilson's disease, Alpha-1 Antitrypsin deficiency, or Glycogen storage disease.
• Skin conditions which could be aggravated by MREL (i.e. Epidermolysis bullosa).
Autoimmune Liver Disease, Autoimmune Hepatitis, Primary Sclerosing Cholangitis
Impact of Short and Mistimed Sleep on Adolescents With ADHD: The Adolescent Attention and Circadian Timing Study (AACT)
- teensleep@cchmc.org
AACT
ALL
13 years to 17 years old
NA
NCT07684417
Inclusion Criteria:
* Ages 13-17 years at time of informed consent/assent
* Based on semi-structured clinical interview, participants must meet full DSM-5 criteria for ADHD inattentive or ADHD combined presentation.
Exclusion Criteria:
* Non-traditional school setting (morning-afternoon Monday-Friday).
* Exclusionary diagnoses. We will exclude adolescents with known intellectual disability, autism spectrum disorder, psychosis, bipolar disorder, or neurologic conditions (e.g., epilepsy), per caregiver-report.
* Exclusionary sleep disorders. We will exclude adolescents with symptoms of obstructive sleep apnea or periodic limb movement disorder based on published cutoffs on a validated questionnaire.
* High caffeine intake. To promote adherence to directives not to consume caffeine the day of office visits without withdrawal effects, adolescents with daily intake of \>1 coffee or "energy drink" or \>2 caffeinated sodas per day based on caregiver- and adolescent-report will be excluded.
* Unwillingness or inability to take part in study procedures (e.g., visits, prescribed sleep conditions).
* Medication use or unwillingness to discontinue melatonin and/or stimulant medications during the 3-week study protocol.
* Refusal to refrain from automobile driving during the sleep restriction condition.
* "Intermediate" Chronotypes (neither morning larks nor night owls) based on habitual sleep timing on nights when adolescent has no morning obligations such as school or work. BEHAVIORAL: Aligned sleep extension, BEHAVIORAL: Misaligned sleep extension
ADHD