This phase I trial tests the safety, side effects and best dose of asciminib as maintenance treatment for adults with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) who have undergone cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR) T cell therapy. Maintenance treatment is given to help keep cancer from coming back after it has disappeared following initial therapy. Asciminib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving asciminib may be safe and tolerable as maintenance treatment for adult patients with Philadelphia chromosome positive ALL who have undergone cellular therapies.
PRE-SCREENING: Documented informed consent of the participant and/or legally authorized representative
PRE-SCREENING: Age ≥ 18 years
PRE-SCREENING: Participant was diagnosed with Ph+ ALL according to World Health Organization criteria. The BCR::ABL1 translocation may be detected by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), next generation sequencing (NGS), or cytogenetics at least once any time prior to cellular therapy. Participants may have p190 or p220 isoform, and participants with T315I mutation are not excluded
Arm 1: Have a date for HSCT scheduled within the next 30 days or have received HSCT within the last 30 days. Note: all HSCT donors, conditioning regimens, and GVHD prophylaxis regimens will be acceptable.
Prior treatment failure with asciminib
Treatment with strong inducers of CYP3A is not allowed and should be switched to an alternative at least 1 week prior to the start of study treatment
ARM 1: Treatment with prior HSCT is allowed
ARM 2: Treatment with prior CAR T cell therapy is allowed
Single group
Asciminib
DrugGiven PO
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Echocardiography Test
Procedure/SurgeryUndergo echocardiography
Survey Administration
Other interventionAncillary studies
Incidence of adverse events
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The toxicity/adverse event information recorded on each subject will include type, severity, duration, attribution/ association with the study agent by arm and cycle. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection. Point estimates and 90% confidence intervals will be provided.
Number of patients who have completed at least 3 cycles of asciminib and have taken ≥ 70% planned doses in each cycle post cellular therapy
The protocol therapy will be deemed feasible if \> 70% or higher of patients meet this feasibility criteria. Point estimates and 90% confidence intervals will be provided.
Duration of remission
Point estimates and 90% confidence intervals will be provided.
Relapse including minimal residual disease (MRD) relapsed
MRD relapse assed by polymerase chain reaction (PCR) and flow cytometry. MRD relapse is defined as detectable leukemic cells at \> 0.01% in morphological remission bone marrow. However, due to rate of false positivity of PCR BCR::ABL1, confirmation is required by either positive MRD flow or/and clonoSEQ \> 0.01%. Will be calculated using the competing risk method. Point estimates and 90% confidence intervals will be provided.
Relapse free survival
Kaplan-Meier curves will be used for survival endpoints. Point estimates and 90% confidence intervals will be provided.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
