Venetoclax Basket Trial for High Risk Hematologic Malignancies

Conditions

• Acute Leukemia of Ambiguous Lineage
• Acute Leukemia of Ambiguous Lineage in Relapse
• Acute Lymphoblastic Leukemia With Failed Remission
• Acute Lymphoblastic Leukemia, in Relapse
• Lymphoblastic Lymphoma, Refractory
• Lymphoblastic Lymphoma, in Relapse
• Myelodysplastic Syndromes, Previously Treated
• Myelodysplastic Syndromes, Secondary
• Myelodysplastic Syndromes, de Novo
• Therapy-Related Myelodysplastic Syndrome
• Treatment-Related Acute Myeloid Leukemia

Eligibility Criteria

Sex

ALL

Age

1 Year - 40 Years

Healthy Volunteers

Not accepted

Interventions

• Venetoclax — DRUG
  Tablet taken orally
• Azacitidine — DRUG
  Taken intravenously
• Cytarabine — DRUG
  Lumbar Puncture
• Methotrexate — DRUG
  Lumbar Puncture
• Hydrocortisone — DRUG
  Lumbar Puncture
• Leucovorin — DRUG
  Taken Orally or intravenously
• Dexamethasone — DRUG
  Taken Orally or intravenously
• Vincristine — DRUG
  Taken intravenously
• Doxorubicin — DRUG
  Taken intravenously
• Dexrazoxane — DRUG
  Taken intravenously
• Calaspargase Pegol — DRUG
  Taken intravenously
• Erwinia asparaginase — DRUG
  Given as intramuscular injection

Study Details

This trial is evaluating the safety and tolerability of venetoclax with chemotherapy in pediatric and young adult patients with hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia derived from myelodysplastic syndrome (MDS/AML), and acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). The names of the study drugs involved in this study are below. Please note this is a list for the study as a whole, participants will receive drugs according to disease cohort. * Venetoclax * Azacitidine * Cytarabine * Methotrexate * Hydrocortisone * Leucovorin * Dexamethasone * Vincristine * Doxorubicin * Dexrazoxane * Calaspargase pegol * Hydrocortisone

Key Dates

Start date

Mar 29, 2023

Status verified

Mar 2026

Primary completion

Jul 2, 2028

Completion

Jul 2, 2030

Study Design

Enrollment

30 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A
  For Part 1, participants will receive: * Patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). It is expected that up to 18 people will participate in Part 1 (Dose Determination) and an additional 14-20 people will participate in Part 2 (Dose Expansion) of this cohort Treatment cycle is approximately 28 days for up to 4 cycles * Venetoclax-once daily on predetermined days per protocol * Azacitidine-once daily on predetermined days per protocol * Cytarabine, Methotrexate, Hydrocortisone and Leucovorin will be given only if MDS/leukemia cells are detected in spinal fluid per determination of treating physician
• Experimental: Cohort B
  Patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) with an underlying genetic condition that increases their risk for developing treatment-related toxicities. It is expected that up to 18 people will participate in Part 1 (Dose Determination) and an additional 6 people will participate in Part 2 (Dose Expansion) of this cohort. * Venetoclax-once daily on predetermined days per protocol * Azacitidine-once daily on predetermined days per protocol * Cytarabine, Methotrexate, Hydrocortisone and Leucovorin will be given only if MDS/leukemia cells are detected in spinal fluid per determination of treating physician
• Experimental: Cohort C
  Patients with relapsed/refractory acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LBL) or acute leuekmai of ambiguous lineage. It is expected that up to 18 people will participate in Part 1 (Dose Determination) and an additional 12 people will participate in Part 2 (Dose Expansion) of this cohort. Cohort C: Treatment cycle is approximately 32 days for one cycle and will be a single treatment cycle: Dosage, duration and timings as outlined in protocol. * Venetoclax * Dexamethasone * Vincristine * Doxorubicin * Dexrazoxane * Calaspargase pegol ---Short acting Erwinia preparations (recombinant or native Erwinia asparaginase) may be used for participants with known pegaspargase or calaspargase pegol allergy * Cytarabine * Methotrexate * Hydrocortisone * Leucovorin- \*Cytarabine, Methotrexate, Hydrocortisone and Leucovorin may be given more frequently if leukemia/lymphoma cells are detected in spinal fluid),

Primary Outcome Measure

Maximum tolerated dose (MTD) [ Time Frame: MTD determined during first cycle of treatment (Cohorts A&B: max. 35 Days; Cohort C: 32 days) ]

Central Contacts

• Andrew E Place, MD, PhD
  617-632-2313
  [email protected]
• Jessica A Pollard, MD, PhD
  617-632-4321
  [email protected]

Locations (5)

Find similar trials in San Francisco, CA

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