Pediatric-Inspired Chemotherapy Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT04845035|
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : May 12, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia||Drug: Dasatinib Drug: Ponatinib Drug: Berlin-Frankfurt-Münster Chemotherapy Drug: Methotrexate and Cytarabine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Using a BFM Regimen Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia|
|Estimated Study Start Date :||July 2022|
|Estimated Primary Completion Date :||March 2025|
|Estimated Study Completion Date :||March 2028|
Experimental: BFM + Tyrosine Kinase Inhibitor
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.
Drug: Berlin-Frankfurt-Münster Chemotherapy
with varied cycles, including Daunorubicin, Vincristine, Prednisone, Pegaspargase, Rituximab, Cytarabine, Mercaptopurine, Cyclophosphamide, Methotrexate, Doxorubicin, Thioguanine, and Dexamethasone
Drug: Methotrexate and Cytarabine
- Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM [ Time Frame: 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.
- Rate of Adverse Events related to Dasatinib and Ponatinib [ Time Frame: 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 pancreatitis
- Percentage of participants who begin ponatinib post-induction that complete at least one cycle. [ Time Frame: 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 [ Time Frame: 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
- Complete cytogenic remission (CCyR) rate post induction [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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). [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04845035
|United States, Michigan|
|University of Michigan Rogel Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Cancer AnswerLine 800-865-1125 CancerAnswerLine@med.umich.edu|
|Principal Investigator: Patrick Burke, MD|
|Principal Investigator:||Patrick Burke, MD||University of Michigan|