Venetoclax Basket Trial for High Risk Hematologic Malignancies

Recruiting now · Phase 1

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

In brief

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 facts

Study ID

NCT05292664

Run by

Andrew E. Place, MD

People needed

30

Starts

2023-03-29

Expected to finish

2030-07-02

Last updated by the study team

2026-03-12

Who can join

Age: 1 and older, up to 40. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Cohort A Inclusion Criteria:
• MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria:
• MDS with excess blasts (>10%)
• MDS with blasts <10% with high-risk features
• MDS refractory to initial treatment
• Relapsed MDS
• MDS/AML: May be newly diagnosed or relapsed/refractory disease.
• Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease.
• Note: MDS or MDS/AML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment.
• Age ≤ 40 years of age, except the following subjects that must be <18 years to enroll
• Subjects with MDS/AML that have not received prior therapy
• Subjects enrolled onto Dose level -2.
• Lansky/Karnofsky performance status ≥ 50%
• Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria:
• Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period
• Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate)
• Hydroxyurea
• Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
• Radiation therapy (XRT):
• Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
• XRT for chloroma does not require a washout period.
• Palliative XRT does not require a washout
• Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. 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.
• Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.
• Monoclonal antibodies: At least 3 half-lives of the antibody

You may not qualify if…

• Cohort A Exclusion Criteria
• Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
• Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
• Individuals with known active hepatitis; baseline testing not required.
• Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
• Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
• Pregnant or nursing women are excluded.
• Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Cohort B Exclusion Criteria
• Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
• Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
• Individuals with known active hepatitis; baseline testing not required.
• Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
• Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
• Pregnant or nursing women are excluded.
• Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Cohort C Exclusion Criteria
• Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
• Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 90 days from stem cell infusion
• Individuals with known active hepatitis; baseline testing not required.
• Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
• Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
• Pregnant or nursing women are excluded
• Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of pegaspargase or calaspargase pegol. Participants with a history of allergy to pegylated formulation of asparasginase are allowed on study but should receive commercial supply of asparaginase Erwinia chrysanthemi (Erwinaze), crisantaspase (Erwinase), or asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) instead of calaspargase pegol (see Sections 6.2.6 and 6.2.7). Individuals with a history of allergy to Erwinaze, Erwinase or Rylaze are excluded from the study.

Where it is running

• University of California San Francisco-Benioff Children's Hospital — San Francisco, California, United States (enrolling)
• Children's Hospital Colorado — Aurora, Colorado, United States (enrolling)
• Children's Healthcare of Atlanta at Arthur M. Blank Hospital — Atlanta, Georgia, United States (enrolling)
• Ann & Robert H Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

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