This phase II trial is to answer the question of "can adding the study drug, asciminib to usual treatment improve how chemotherapy works against Ph+ Acute Lymphoblastic Leukemia (ALL) and is this approach better than the usual approach for Ph+ALL?"
PRIMARY OBJECTIVES: I. To assess the rate of major molecular remission (MMR) by polymerase chain reaction (PCR) for BCR-ABL at day 85 in newly diagnosed participants with Philadelphia-chromosome positive Ph+ acute lymphoblastic leukemia (ALL) treated with asciminib, dasatinib and prednisone. SECONDARY OBJECTIVES: I. To estimate the rate of complete remission (with and without complete count recovery, CR/CRi) at day 85 in this participant population. II. To describe disease-free survival (DFS) in this participant population. III. To estimate overall survival (OS) in this participant population. IV. To estimate the frequency and severity of toxicities in this participant population. V. To estimate the rate of measurable residual disease remission by flow cytometry (MRD Flow) at day 85 in this participant population. VI. To compare rates of MMR by PCR and MRD flow remission in this participant population. VII. Among participants who achieve MMR, to estimate the cumulative incidence of relapse from MMR in this participant population. VIII. To describe attainment and failure of MR3.0, MR4.0 and MR4.5 at day 85 in this participant population. IX. To estimate the rate of complete remission with undetectable MRD levels by flow cytometry (MRDundetectable CR) in this participant population. X. To estimate duration of MMR in this participant population. XI. To estimate duration of MR4.0 in this participant population. XII. To estimate time to treatment failure in this participant population. XIII. To describe event-free survival (EFS) in this participant population. TRANSLATIONAL MEDICINE OBJECTIVES: I. To evaluate and describe the genes and pathways associated with response (molecular response) to therapy. II. To describe the spectrum of mutations observed, and the timing of their emergence, in resistant/relapse samples. III. To bank specimens for future correlative studies. OUTLINE: Patients will have their phase of treatment determined by their responses tested by blood and bone marrow tests. PHASE 1 TREATMENT (INDUCTION): Phase 1 treatment may last up to 12 weeks. Patients will start with 4 weeks of treatment. Patients will receive Asciminib every day with a combination of other drugs. After 4 weeks of Phase 1 treatment, patients will be testing to see how the leukemia is responding. If There are no more signs of leukemia, the patients will receive 8 more weeks of Phase 1 treatment. if there are still signs of leukemia, patients will receive 4 more weeks of Phase 1 treatment and then will be tested again. If there are no signs of leukemia, they will receive 4 more weeks of Phase 1 treatment for a total of 12 weeks. If there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, the patients will start Re-induction treatment. Re-Induction treatment may last up to 12 weeks. Patients will start with 6 weeks of treatment. Patients will receive Blinatumomab every day for 28 days and Dasatinib every day for 42 days. After weeks of treatment, patients are tested and if there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, patients will repeat 6 weeks of Re-induction treatment. After repeating 6 weeks of Re-induction treatment if there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, patients will stop treatment in the study. PHASE 2 TREATMENT (POST-REMISSION): Phase 2 treatment will last up to 18 weeks. Patients will receive treatment in cycles of 42 days. There are 3 cycles of Phase 2 treatment. Patients will receive Blinatumomab every day for days 1-28 of each cycle and Dasatinib every day of each cycle. After Phase 2 treatment, patients will be tested. If there are no signs of leukemia, patients will start Phase 3 treatment. If there are signs of leukemia, patients will stop treatment in the study. PHASE 3 TREATMENT (MAINTENANCE): Patients will receive maintenance treatment for as long as it helps them. Phase 3 Treatment is given in 28-day cycles. Patients will receive Asciminib every day of each cycle, for up to five years from the time they started the study. Patients will take Dastinib every day of each cycle for as long as it helps them and Prednisone days 1-5 of each cycle for 18 cycles. Patients will stop treatment if the leukemia comes back or if side effects become too severe. After completion of study treatment, patients are followed up on every 3 months for the first two years, and every 6 months until five years after treatment ends.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Asciminib, Dasatinib, Prednisone, and Methotrexate
Blinatumomab, Dasatinib, Methotrexate, and Dexamethasone
Blinatumomab, Dasatinib, Methotrexate and Dexamethasone
University of Cincinnati Cancer Ctr-UC Medical Ctr
Cincinnati, Ohio, United States
Baptist Memorial Health Care
Memphis, Tennessee, United States
Major molecular remission by polymerase chain reaction for BCR-ABL
Major molecular remission (MMR), also known as MR3.0, is defined as BCR-ABL transcript levels (expressed as a percentage compared with the ABL control gene) ≤ 0.1% based on PCR at day 85.
Time frame: Up to 100 days after treatment start
Rate of Complete Remission (with and without complete count recovery, CR/CRi)
Complete response rate is measured by the number of participants achieving complete remission (CR) or complete remission with incomplete platelet recovery (CRi) rate. CR is defined as having \<5% marrow aspirate blasts, ANC \>1,000/mcL, platelets \> 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be \<= 100,000/mcL and/or ANC \<=1,000/mcL.
Time frame: Up to 100 days after treatment start
Disease-free Survival
Measured from the date the participant first achieves CR or CRi until relapse from CR/CRi or death from any cause. Observations will be censored on the day of last contact for participants last known to be alive in CR/CRi.
Time frame: Up to 5 years.
Overall Survival
From the day of Step 1 registration on study until death from any cause with observations censored on the day of last contact for participants last known to be alive.
Time frame: Up to 5 years
Incidence of Adverse Events
Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event. Adverse Events are reported using CTCAE v 5.0.
Time frame: Up to 5 years
Rate of Measurable Residual Disease Remission by Flow Cytometry (MRD Flow)
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Asciminib, Dasatinib, Prednisone, and Methotrexate
Measurable residual disease (MRD) remission is defined as undetectable MRD levels by flow cytometry.
Time frame: Up to 100 days after treatment start
Major molecular remission and measurable residual disease remission by flow cytometry
Comparison of rates of major molecular remission by polymerase chain reaction (MMR) and measurable residual disease remission by flow cytometry (MRD Flow).
Time frame: Up to 100 days after treatment start
Relapse from Major Molecular Remission (MMR)
Cumulative incidence of relapse from MMR, defined as BCR-ABL transcript levels (expressed as a percentage compared with the ABL control gene) \> 0.1% based on PCR.
Time frame: Up to 5 years
Molecular Response 4.0 (MR4.0) Rate at Day 85
MR4.0 is defined as a 4.0-log reduction, relative to baseline, of the BCR-ABL/ABL ratio based on PCR. This response is equivalent to a value of \<= 0.01% when reported on the International Scale.
Time frame: Up to 100 days after treatment start
Molecular Response 4.5 Rate at Day 85
MR4.5 is defined as a 4.5-log reduction, relative to baseline, of the BCR-ABL/ABL ratio based on PCR. This response is equivalent to a value of \<= 0.0032% when reported on the International Scale.
Time frame: Up to 100 days after treatment start
Rate of Complete Remission with Undetectable MRD by Flow Cytometry
Number of participants meeting criteria for complete remission (CR) and measurable residual disease flow remission (MRD Flow).
Time frame: Up to 5 years
Duration of Major Molecular Remission by PCR
Measured from the date the participant first achieves MMR until relapse from MMR or death from any cause. Observations will be censored on the day of last contact for participants last known to be alive in MMR.
Time frame: Up to 5 years
Duration of MR4.0 by PCR
Measured from the date the participant first achieves MR4.0 until relapse from MR4.0 or death from any cause. Observations will be censored on the day of last contact for participants last known to be alive in MR4.0.
Time frame: Up to 5 years
Time to Treatment Failure
From the day of Step 1 registration on study until treatment failure, or death due to any cause. Observations will be censored on the day of last contact for participants last known to be alive and failure free.
Time frame: Up to 5 years
Event-free Survival
From the day of Step 1 registration on study until failure to achieve CR/CRi following induction or re-induction, relapse from CR/CRi, or death due to any cause. Observations will be censored on the day of last contact for participants last known to be alive in CR/CRi.
Time frame: Up to 5 years.