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
Categories (click each to see list of all clinical trials associated with that category): Pediatric (PEDONC)
Current Status: Open
Phase: II (Cancer Control)
Principal Investigator: Beck, Jill
Contact Information:
Angie Boettner
aboettner@unmc.edu
Eligibility: https://clinicaltrials.gov/study/NCT06317662?term=NCT06317662&rank=1#study-overview
Summary
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 compare event free survival (EFS) rates of infants with KMT2A-R ALL treated on arm B to those treated on arm A.
II. To compare 3-year EFS of infants with KMT2A-R ALL treated on arm A to historical controls.
III. To determine the feasibility of treating infants with KMT2A-G ALL with a Children's Oncology Group (COG) high-risk ALL chemotherapy backbone and two cycles of blinatumomab and describe their outcomes.
IV. To characterize the pharmacokinetics (PK) of venetoclax in infants.
EXPLORATORY OBJECTIVES:
I. To describe 3-year EFS of infants with KMT2A-R ALL treated on arm B. II. To describe 3-year EFS of infants with KMT2A-G ALL treated on arm C. III. To evaluate the use of high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized flow cytometry.
IV. To characterize the PK of calaspargase pegol-mknl in infants with ALL. V. To report the incidence of CD19 negative relapse and myeloid switch relapse with protocol therapy.
VI. To evaluate the impact of venetoclax in combination with chemotherapy on T-cell subsets and function.
VII. To describe the feasibility of T-cell collection and success of T-cell manufacturing for infants with KMT2A-R ALL who receive chimeric antigen receptor (CAR) T- cell therapy after coming off protocol therapy.
VIII. To determine predictors of response and resistance to venetoclax and overall protocol therapy.
IX. To evaluate the impact of subsequent anti-cancer therapy on overall survival after coming off protocol therapy.