A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax
National Cancer Institute (NCI)
Summary
This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
Description
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of venetoclax in addition to a standard chemotherapy backbone and two cycles of blinatumomab in infants (aged 365 days or less at diagnosis) with newly diagnosed KMT2A-R ALL. II. To determine in a randomized manner if the addition of venetoclax to induction chemotherapy improves end of induction minimal residual disease (MRD)-negative remission rates in infants with KMT2A-R ALL. SECONDARY OBJECTIVES: I. To estimate the MRD-negative remission rate for all eligible infants with KMT2A-R ALL treated with venetoclax at the recommend…
Eligibility
- Age range
- Up to 1 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321 * Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age at the time of enrollment * Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype…
Interventions
- DrugAsparaginase Erwinia chrysanthemi
Given recombinant crisantaspase IM or crisantaspase IM or IV
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- BiologicalBlinatumomab
Given IV
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- DrugCalaspargase Pegol
Given IV
- ProcedureComputed Tomography
Undergo CT
- DrugCyclophosphamide
Locations (108)
- Children's Hospital of AlabamaBirmingham, Alabama
- Providence Alaska Medical CenterAnchorage, Alaska
- Banner Children's at DesertMesa, Arizona
- Arkansas Children's HospitalLittle Rock, Arkansas
- Loma Linda University Medical CenterLoma Linda, California
- Miller Children's and Women's Hospital Long BeachLong Beach, California