This study will combine a standard, pediatric-inspired, chemotherapy regimen with the tyrosine kinase inhibitors (TKIs) Dasatinib and Ponatinib to treat adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. There are two age groups/cohorts: * participants aged 18 to 59 years * participants aged 60 years and older One tyrosine kinase inhibitor (TKI), either Dasatinib or Ponatinib, will be administered in each of the respective chemotherapy cycles. The TKI (either Dasatinib or Ponatinib) administered in a given cycle of chemotherapy will be dictated by the given cycle's standard chemotherapy, in order to minimize overlapping side effects of the chemotherapy and TKI. The dosages of the standard chemotherapy agents, as well as the tyrosine kinase inhibitors (TKIs)--Dasatinib and Ponatinib--have been adjusted for each age group to allow continuous administration of these TKIs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
By mouth
By mouth
with varied cycles, including Daunorubicin, Vincristine, Prednisone, Pegaspargase, Rituximab, Cytarabine, Mercaptopurine, Cyclophosphamide, Methotrexate, Doxorubicin, Thioguanine, and Dexamethasone
Intrathecal
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM
CMR will be assessed by minimal residual disease (MRD)-negative status, using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis from bone marrow aspirates, after 1 cycle of induction therapy with Berlin-Frankfurt-Münster (BFM) protocol and Dasatinib.
Time frame: Post day 36; up to day 43
Rate of Adverse Events related to Dasatinib and Ponatinib
Per NCI CTCAE v5.0 toxicity data, specifically: * for dasatinib: pulmonary hypertension (any grade) or grade ≥ 3 serositis/volume overload. * for ponatinib: arterial embolism (any grade) and grade ≥ 3 venous thromboembolism, heart failure, or pancreatitis
Time frame: 30 days after last treatment, up to approximately 3 years
Percentage of participants who begin ponatinib post-induction that complete at least one cycle.
Feasibility will be assessed by the percentage, among patients who begin the ponatinib post-induction regimen, that complete at least one cycle. Completion is defined as the ability to tolerate ≥ 80% dose intensity of all prescribed anti-cancer agents per cycle of ponatinib initiated.
Time frame: At 18 weeks
Complete hematologic (morphologic) remission (CHR) rate after induction
Bone marrow assessed by morphologic review of both the aspirate smear and core biopsy
Time frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
Complete cytogenic remission (CCyR) rate post induction
Bone marrow aspirate assessed by karyotype and/or fluorescence in situ hybridization (FISH).
Time frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
Complete molecular remission (CMR) rate
Bone marrow aspirate analyzed by RT-qPCR.
Time frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
Disease-free survival (DFS)
Disease-Free Survival (DFS) is defined as the duration of time from attainment of CR (morphologic remission, hematologic remission, etc) to Morphologic Relapse (Relapsed Disease) or Death.
Time frame: up to five years after end of study treatment (approximately 8 years)
Overall survival (OS).
Overall Survival (OS) is defined as the length of time from the date of diagnosis that patients diagnosed with the disease are still alive.
Time frame: up to five years after end of study treatment (approximately 8 years)
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