StudyFinder
Search Results Within Category "Cancer - Lymphoma - Non-Hodgkin"
10 Study Matches
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
- cancer@cchmc.org
ALL
0 years to 38 years old
NCT06131801
Inclusion Criteria:
* Age: Patients must be \<39 years of age at time of study enrollment
* Diagnosis: Patients may have a diagnosis of any hematologic malignancy
* Central access: Patients must have an existing venous or arterial access line for PK blood draws
* Weight requirement: Patients must weigh at least 5.5 kg at the time of enrollment
* Venetoclax: Patients must be receiving any dose of venetoclax given as a solution made from crushed tablets by mouth (PO) or via nasogastric (NG), or G-tube as prescribed by their treating oncologist.
* Concurrent chemotherapy medications: Patients may receive venetoclax as a single agent or in combination with any other chemotherapeutic agents.
Exclusion Criteria:
* Pregnant women are excluded from this study because venetoclax has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax.
* Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion. OTHER: 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.
Hematologic Malignancy, Leukemia, Lymphoma, Acute Lymphocytic Leukemia, ALL, Acute Myelogenous Leukemia, AML, Chronic Myelogenous Leukemia, CML, Myeloproliferative Neoplasm, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Burkitt Lymphoma, T-cell Lymphoma, B Cell Lymphoma, Peripheral T Cell Lymphoma, Cutaneous B-Cell Lymphoma
Venetoclax, Pediatric AML, Pediatric Relapsed/Refractory AML
A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (T-RRex)
- cancer@cchmc.org
ALL
6 month(s) and over
PHASE2
NCT06514794
Key
Inclusion Criteria:
* Disease Criteria: Evidence of T-ALL or T-LBL, as defined by World Health Organization (WHO) classification, and either relapse/refractory or MRD positive
* Age: Lower age limit of ≥ 6 months; adequate organ function
* Eastern Cooperative Oncology Group (ECOG)/Karnofsky Performance Status 0 or 1/70 and above at Screening.
Key Exclusion Criteria:
* Prior treatment with any anti-CD7 therapy.
* Patients with decompensated hemolytic anemia.
* Presence of Grade 2 to 4 acute or extensive chronic GvHD requiring systemic immunosuppression. Grade 1 GvHD not requiring immunosuppression or Grade 2 skin GvHD if treated with topical therapy only are acceptable. BIOLOGICAL: WU-CART-007
T-cell Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
CAR-T Therapy, Acute Leukemia
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
- cancer@cchmc.org
ALL
12 months to 21 years old
PHASE1
NCT04870944
Inclusion Criteria:
* Parts A and B: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy
* Part A: Patients must have either measurable or evaluable disease
* Part B: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/sex as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography Test, DRUG: FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27-Altered, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Diffuse Midline Glioma, H3 K27-Altered, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Primary Malignant Central Nervous System Neoplasm
A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma (iMATRIX GLO)
Michelle Michelle Anton - Michelle.Anton@cchmc.org
ALL
6 months to 30 years old
PHASE1
NCT05533775
Inclusion Criteria:
* Age 6 months to \< 18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to \< 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study
* Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B
* Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B
* Measurable disease, defined as: At least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension; or percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates
* Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales: Participants \< 16 years old: Lansky Performance Status ≥ 50%; Participants ≥ 16 years old: Karnofsky Performance Status ≥ 50%
* Adequate bone marrow, liver, and renal function
* Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV)
* Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ≥200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
* Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
* Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods
Exclusion Criteria:
* Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
* Receipt of glofitamab prior to study enrollment
* Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
* Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
* Participants with active infections which are not resolved prior to Day 1 of Cycle 1
* Prior solid organ transplantation
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or chronic active Epstein-Barr viral infection (CAEBV)
* Active autoimmune disease requiring treatment
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products, except if the participant was able to safely receive it after initial administration (consider consultation with Medical Monitor)
* History of confirmed progressive multifocal leukoencephalopathy
* Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
* Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
* Major surgery or significant traumatic injury \< 28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
* Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment
* Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug DRUG: Obinutuzumab, DRUG: Glofitamab, DRUG: Rituximab, DRUG: Ifosfamide, DRUG: Carboplatin, DRUG: Etoposide, DRUG: Tocilizumab
Mature B-Cell Non-Hodgkin Lymphoma
Relapsed, Refractory, Pediatrics, B-NHL
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
- cancer@cchmc.org
ALL
NCT01790152
Inclusion Criteria:
Study Strata I, II, and III are closed for further patient entry as of March 31, 2021. The study remains open for existing medical record submission of Stratum IV
* STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
* Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
* STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma \[P9404, high-risk DFCI 95-01\] or Hodgkin lymphoma \[P9425/P9426\])
* STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
* STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest \[also includes fields directed towards the neck, upper abdomen, or spine\], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
* STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's \[COG?s\] Statistics and Data Center \[SDC\] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (IRB) specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims; patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution)
* STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
* STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM III: OSTEOSARCOMA SURVIVORS
* Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
* Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
* Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
* \< 31 years of age at time of initial osteosarcoma diagnosis
* Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
* No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction \>= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction \>= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
* Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m\^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
* No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
* No exposure to DRZ at any point in time
* All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3
* Individuals diagnosed with cancer prior to age 21 years, who required treatment with chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after completing anti-cancer-therapy for at least 1 year
* Must have screening echocardiograms for heart function as part of cancer therapy and off-therapy evaluations available (Digital Imaging and Communications in Medicine \[DICOM\] format). Images from Video Home System (VHS) tapes and reports only (without images) are not suitable
* Cannot have a known history of congenital heart disease (patent foramen ovale remain eligible) or underlying genetic syndrome associated with abnormal cardiovascular development or health (e.g., down syndrome)
* Based on echocardiography, must have either left ventricular fractional shortening =\< 28.0% or ejection fraction =\< 50.0% on at least two occasions, with at least one of these measurements occurring after cancer therapy completion and be in the absence of sepsis or any uncontrolled infection
* If the fractional shortening or ejection fraction criteria is only met on one occasion, this must be after cancer therapy completion, be in the absence of sepsis or any uncontrolled infection, and the patient must have subsequently started on chronic medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme \[ACE\]-inhibitor, angiotensin receptor blocker) lasting at least 6 months
* For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Assessment of Therapy Complications, OTHER: Laboratory Biomarker Analysis, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma in Remission, Leukemia in Remission, Lymphoblastic Lymphoma, Osteosarcoma, Recurrent Leukemia, Recurrent Lymphoma, Recurrent Malignant Neoplasm
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
- cancer@cchmc.org
ALL
365 days to 25 years old
PHASE3
NCT03959085
Inclusion Criteria:
* B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
* APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
* Patients must be \> 365 days and \< 25 years of age
* Initial white blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-9.99 years: WBC \>= 50,000/uL
* Age 10-24.99 years: Any WBC
* Age 1-9.99 years: WBC \< 50,000/uL with one or more of the following:
* Testicular leukemia
* CNS leukemia (CNS3)
* Steroid pretreatment.
* Initial white blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
* Patient has newly diagnosed B-ALL or MPAL (by World Health Organization \[WHO\] 2016 criteria) with \>= 25% blasts on a bone marrow (BM) aspirate;
* OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
* OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
* Patient has newly diagnosed B-LLy Murphy stages III or IV.
* Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
* Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
* Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. Note that once cerebrospinal fluid (CSF) has been collected, protocol therapy can be initiated while final determination of CNS status is pending. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
* Direct bilirubin \< 2.0 mg/dL (34 micromoles/L)
* Alanine aminotransferase (ALT) ≤ 10x upper limit of normal (ULN). For the purposes of this study, the ULN for ALT is defined as 45 U/L
* Exceptions to this include patients with known Gilbert's Syndrome, or those with hepatic involvement from leukemic or lymphomatous infiltration
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Exclusion Criteria:
* Patients with Down syndrome are not eligible
* With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
* Patients who have received \> 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
* Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing \> 1,000/uL circulating leukemia cells.
* Patients with acute undifferentiated leukemia (AUL) are not eligible.
* For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:
* T-lymphoblastic lymphoma.
* Morphologically unclassifiable lymphoma.
* Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
* Patients with known Charcot-Marie-Tooth disease.
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
* Patients requiring radiation at diagnosis.
* 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.
* Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males. PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Inotuzumab Ozogamicin, DRUG: Leucovorin Calcium, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Pegaspargase, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, DRUG: Prednisone, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia
Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
- cancer@cchmc.org
ALL
12 months to 30 years old
PHASE1
NCT04851119
Inclusion Criteria:
* PART A: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* PART B: Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
* PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
* PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
* PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Non-Hodgkin lymphoma patients
* A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \[6MP\], and/or methotrexate)
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
* NOTE: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days.
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).
* External beam radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to tegavivint
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \>= 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age; maximum serum creatinine
* Age 1 to \< 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
* Age 2 to \< 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
* Age 6 to \< 10 years; 1 mg/dL (male); 1 mg/dL (female)
* Age 10 to \< 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
* Age 13 to \< 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
* Age \>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
* PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Albumin \>= 2 g/dL (within 7 days prior to enrollment)
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
* Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
* Patients who have received denosumab within 180 days prior to study enrollment will be excluded
* Patients with primary brain tumors are ineligible
* Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
* Patients with a disorder associated with abnormal bone metabolism will be excluded
* Patients with grade \>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
* Patients with vitamin D \< 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
* Patients with pre-existing grade 3 osteoporosis are excluded
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Dual X-ray Absorptiometry, DRUG: Tegavivint, PROCEDURE: X-Ray Imaging
Colorectal Carcinoma, Endometrial Carcinoma, Melanoma, Neuroblastoma, Ovarian Carcinoma, Pancreatic Ductal Adenocarcinoma, Recurrent Desmoid Fibromatosis, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Hepatocellular Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Refractory Desmoid Fibromatosis, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Hepatocellular Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Solid Pseudopapillary Neoplasm of the Pancreas, Wilms Tumor
Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies
Charles Alexander - Charles.Alexander@cchmc.org
ALL
1 year to 21 years old
PHASE1
NCT05476770
Inclusion Criteria:
Age
* Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment.
Diagnosis
* Relapsed and/or refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma).
* Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution.
Disease Status:
Monotherapy, Part 1
* Second or greater relapse; or
* Refractory after 2 or more chemotherapy cycles; or
* First relapse after primary chemotherapy-refractory disease; or
* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
Combination therapy, Part 2
* First or greater relapse; or
* Refractory after 2 or more chemotherapy cycles; or
* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
For relapsed/refractory leukemia, patients must have:
* \>5% blasts in the bone marrow aspirate or biopsy by morphology or flow cytometry
* Patients with 1% - 5% blasts are eligible for Part 2, Cohort C (only), if A single bone marrow sample with flow cytometry and at least one other test (e.g. karyotype, FISH, PCR, or NGS) shows ≥ 1% leukemic blasts and/or flow cytometry demonstrates a stable or rising level of disease on two serial bone marrows.
For relapsed/refractory non-Hodgkin or Hodgkin lymphoma, patients must have:
* Histologic verification of relapse
* Measurable disease documented by radiographic criteria or bone marrow
* Patients in Part 1 may have sites of non-CNS extramedullary disease, but no CNS disease. Patients in Part 2 may have CNS disease and/or other non-CNS extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
* Patients with Down syndrome are eligible to participate in Part 1 only.
Performance Level
* Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age (See Appendix I for Performance Scales). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Prior Therapy
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria.
Myelosuppressive chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 day must have elapsed since the completion of myelosuppressive therapy. However, individuals may receive any of the following medications within 14 days without a "wash-out period":
* Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
* "Maintenance-style" therapy: therapy including vincristine (dosed a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed a maximum of one-time weekly), intrathecal therapy (dosed a maximum of one-time weekly) and/or dexamethasone (dosed at ≤3 mg/m2/dose twice daily) or prednisone (dosed at ≤20 mg/m2/dose twice daily) can be continued for up to 24 hours prior to entering the study.
* Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
* Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
* Monoclonal antibodies: Maximum of 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody.
* Immunotherapy: At least 30 days from last infusion of chimeric antigen receptor T cell (CART) therapy or tumor vaccine.
* Radiation Therapy (XRT):
• ≥ 84 days must have passed, from the end of therapy, if patient received prior total body irradiation (TBI).
• ≥ 42 days must have passed, from the end of therapy, if patient received craniospinal irradiation (CSI).
• ≥ 14 days must have passed after whole brain radiotherapy or stereotactic radiation therapy.
• No washout period is required for: i. Extramedullary site other than CNS that is a maximum 10 x 10 cm total radiation non-CNS field. If the field is \> 10 x 10 cm, a 14-day washout period is required. ii. Local ocular radiotherapy as long as subject has measurable/evaluable disease outside the radiation port. * Patients that have received other non-tagraxofusp CD123 targeting agents are eligible. Patients that have previously received tagraxofusp are not eligible. Organ Function Requirements Adequate Bone Marrow Function Defined as: * Patients should not be known to be refractory to red blood cell or platelet transfusions. * Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be ≥20,000/mm3 to initiate therapy (may receive platelet transfusions). Adequate Renal Function Defined as: * Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below: Maximum Serum Creatinine (mg/dL): * 1 to \< 2 years old - Male: 0.6, Female: 0.6 * 2 to \< 6 years old - Male:0.8, Female: 0.8 * 6 to \< 10 years old - Male: 1, Female: 1 * 10 to \< 13 years old - Male: 1.2, Female: 1.2 * 13 to \< 16 years old - Male: 1.5, Female: 1.4 * ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined as: * Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x institutional upper limit of normal for age * SGPT (ALT) and SGOT (AST) must be less than 3x institutional upper limit of normal. * Serum albumin ≥3.2 g/dL (albumin infusion independent). Adequate Cardiac Function Defined as: * Shortening fraction of ≥27% by echocardiogram, or * Ejection fraction of ≥ 50% by gated radionuclide study/echocardiogram. Adequate Pulmonary Function Defined as: * Pulse oximetry \> 94% on room air (\> 90% if at high altitude) * No evidence of dyspnea at rest and no exercise intolerance. Reproductive Function * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 12 weeks after the last dose of tagraxofusp. Exclusion Criteria Disease Status: * Patients with CNS disease are not eligible for Part 1. * Patients with isolated CNS disease are not eligible for Part 1 or Part 2. * Patients with isolated non-CNS disease are eligible for Part 1 and Part 2. Concomitant Medications * Corticosteroids - Patients receiving corticosteroids for disease control who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. * Investigational Drugs - Patients who are currently receiving another investigational drug are not eligible. The definition of "investigational" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia) * Anti-cancer Agents - Patients who are currently receiving or may receive while on therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible \[with the exceptions being laid out in the inclusion criteria under 'Prior Therapy'\]. Intrathecal chemotherapy (at the discretion of the primary oncologist) may be given up to one week prior to the initiation of study treatment (day 1 therapy). * Anti-GVHD or agents to prevent organ rejection post-transplant - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 4 weeks must have elapsed after the last dose of GVHD meds. Infection Criteria - Patients are excluded if they have: * Positive blood culture within 48 hours of study enrollment; * Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability. * A positive fungal culture within 30 days of study enrollment. * Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed. * Patients will be excluded if they have a known allergy to any of the drugs used in the study. * Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results. * Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
DRUG: Tagraxofusp, DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Dexamethasone, DRUG: Vincristine, DRUG: Azacitidine, DRUG: Methotrexate, DRUG: Cytarabine IT, DRUG: Hydrocortisone
Hematologic Malignancy, AML, ALL, BPDCN, MDS, Lymphoblastic Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell, Hodgkin Lymphoma, Mixed Phenotype Acute Leukemia, Acute Undifferentiated Leukemia
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
First-in-human Study of a New Treatment (4A10) for Patients With Relapsed or Hard-to-treat Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma, Focused on Safety and How the Drug Behaves in the Body and Early Signs of Effect. (ALT-101)
- cancer@cchmc.org
ALL
18 years and over
PHASE1
NCT07586618
Key
• Confirmed diagnosis of T/B-ALL or T/B-LL
• Relapsed or refractory disease without curative options
• Adequate organ function and performance status Key
• Patients with CNS3 disease
• Patients with DNA fragility syndromes (e.g., Fanconi, Bloom), trisomy 21 (Down Syndrome)
• Prior exposure to anti-CD127 therapies
• Uncontrolled infections
Inclusion Criteria:
• Confirmed diagnosis of T/B-ALL or T/B-LL
• Relapsed or refractory disease without curative options
• Adequate organ function and performance status Key
Exclusion Criteria:
• Patients with CNS3 disease
• Patients with DNA fragility syndromes (e.g., Fanconi, Bloom), trisomy 21 (Down Syndrome)
• Prior exposure to anti-CD127 therapies
• Uncontrolled infections
DRUG: 4A10
Lymphoblastic Lymphoma, Acute Lymphoblastic Leukemia ALL
Leukemia, Refractory, Relapsed