Pediatric-Inspired Chemotherapy Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Drug: Berlin-Frankfurt-Münster Chemotherapy
- Registration Number
- NCT04845035
- Lead Sponsor
- University of Michigan Rogel Cancer Center
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BFM + Tyrosine Kinase Inhibitor Ponatinib This study has 2 cohorts: participants aged 18 - 59 years and participants aged 60 or more years. Both cohorts receive the same study intervention with dosage adjusted for age. Participants receive the Berlin-Frankfurt-Münster (BFM) protocol plus dasatinib during a two-phase induction and a delayed re-induction. Participants receive the BFM protocol plus ponatinib during post-induction consolidations and maintenance. BFM + Tyrosine Kinase Inhibitor Berlin-Frankfurt-Münster Chemotherapy This study has 2 cohorts: participants aged 18 - 59 years and participants aged 60 or more years. Both cohorts receive the same study intervention with dosage adjusted for age. Participants receive the Berlin-Frankfurt-Münster (BFM) protocol plus dasatinib during a two-phase induction and a delayed re-induction. Participants receive the BFM protocol plus ponatinib during post-induction consolidations and maintenance. BFM + Tyrosine Kinase Inhibitor Methotrexate and Cytarabine This study has 2 cohorts: participants aged 18 - 59 years and participants aged 60 or more years. Both cohorts receive the same study intervention with dosage adjusted for age. Participants receive the Berlin-Frankfurt-Münster (BFM) protocol plus dasatinib during a two-phase induction and a delayed re-induction. Participants receive the BFM protocol plus ponatinib during post-induction consolidations and maintenance. BFM + Tyrosine Kinase Inhibitor Dasatinib This study has 2 cohorts: participants aged 18 - 59 years and participants aged 60 or more years. Both cohorts receive the same study intervention with dosage adjusted for age. Participants receive the Berlin-Frankfurt-Münster (BFM) protocol plus dasatinib during a two-phase induction and a delayed re-induction. Participants receive the BFM protocol plus ponatinib during post-induction consolidations and maintenance.
- Primary Outcome Measures
Name Time Method Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM Post day 36; up to day 43 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.
- Secondary Outcome Measures
Name Time Method Rate of Adverse Events related to Dasatinib and Ponatinib 30 days after last treatment, up to approximately 3 years 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 pancreatitisComplete cytogenic remission (CCyR) rate post induction After Remission Induction Phase I and at end of study treatment, up to approximately 3 years Bone marrow aspirate assessed by karyotype and/or fluorescence in situ hybridization (FISH).
Complete molecular remission (CMR) rate After Remission Induction Phase I and at end of study treatment, up to approximately 3 years Bone marrow aspirate analyzed by RT-qPCR.
Disease-free survival (DFS) up to five years after end of study treatment (approximately 8 years) 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.
Overall survival (OS). up to five years after end of study treatment (approximately 8 years) Overall Survival (OS) is defined as the length of time from the date of diagnosis that patients diagnosed with the disease are still alive.
Percentage of participants who begin ponatinib post-induction that complete at least one cycle. At 18 weeks 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.
Complete hematologic (morphologic) remission (CHR) rate after induction After Remission Induction Phase I and at end of study treatment, up to approximately 3 years Bone marrow assessed by morphologic review of both the aspirate smear and core biopsy
Trial Locations
- Locations (1)
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States