Low-Intensity Chemotherapy and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT03147612|
Recruitment Status : Recruiting
First Posted : May 10, 2017
Last Update Posted : July 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Lymphoblastic Leukemia Acute Myeloid Leukemia With BCR-ABL1 Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Philadelphia Chromosome Positive Recurrent Acute Lymphoblastic Leukemia Refractory Acute Lymphoblastic Leukemia||Drug: Cyclophosphamide Drug: Cytarabine Biological: Filgrastim Drug: Methotrexate Biological: Pegfilgrastim Drug: Ponatinib Biological: Rituximab Drug: Vincristine||Phase 2|
I. To evaluate the complete molecular response (CMR) rate of ponatinib in combination with low-intensity chemotherapy in elderly patients with newly diagnosed Philadelphia chromosome (Ph)-positive and/or BAR-ABL-positive acute lymphoblastic leukemia (ALL).
II. To evaluate the overall response (OR; complete response [CR] + complete response with hematologic improvement [CRi]) in patients with relapsed/refractory disease.
I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete molecular response, event-free survival and overall survival) and safety of the combination regimen.
I. To characterize the frequency of ABL1 kinase domain mutations at diagnosis and to determine their influence on relapse-free survival in patients with Ph+ ALL treated with hyper-CVD plus ponatinib.
II. To determine the impact of recurrent genomic alterations and ribonucleic acid (RNA) expression at diagnosis on relapse free survival (RFS) in patients with Ph+ ALL treated with hyper-CVD plus ponatinib.
III. To investigate the impact of next-generation sequencing-based minimal residual disease assessment on relapse-free survival in patients with Ph+ ALL.
COURSES 1, 3, 5, 7: Patients receive ponatinib orally (PO) once daily (QD) on days 1-14 of course 1 and days 1-28 of subsequent courses, cyclophosphamide intravenously (IV) twice daily (BID) over 3 hours on days 1, 2, and 3, rituximab IV over 4-6 hours on days 1 and 11, receive vincristine IV over 15 minutes on days 1 and 11, pegfilgrastim or filgrastim subcutaneously (SC) daily on day 4, methotrexate intrathecally via spinal tap on day 2 of courses 1, 3, and 5, and cytarabine intrathecally on day 7 of courses 1, 3, and 5.
COURSES 2, 4, 6, 8: Patients receive ponatinib PO QD on days 1-28, methotrexate IV over 24 hours on day 1 and intrathecally on day 8 of courses 2, 4, and 8, cytarabine IV BID over 2-3 hours on days 2 and 3 and intrathecally on day 5 of courses 2, 4, and 6, pegfilgrastim or filgrastim SC daily on day 4, and rituximab IV over 4-6 hours on days 1 and 8.
MAINTENANCE THERAPY: After course 8, if disease has gotten worse, patients receive vincristine IV over 15 minutes on day 1, prednisone PO on days 1-5, and ponatinib PO QD on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
POST-MAINTENANCE THERAPY: Patients receive ponatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of the Combination of Low-Intensity Chemotherapy and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)|
|Actual Study Start Date :||February 8, 2018|
|Estimated Primary Completion Date :||February 8, 2024|
|Estimated Study Completion Date :||February 8, 2024|
Experimental: Treatment (chemotherapy, ponatinib)
See Detailed Description.
Given intrathecally or IV
Given intrathecally or IV
- Complete molecular response (CMR) in newly diagnosed Philadelphia chromosome (Ph)-positive and/or BCR-ABL-positive participants [ Time Frame: Up to 84 days (3 courses) ]The CMR rate within the first 3 courses for cohort 1 or rate within the first 2 courses for cohort 2 will be estimated along with the 95% credible intervals. Similar analyses will be performed for estimating the rate of complete cytogenetic response and major molecular response rates.
- Overall response (OR) in participants with relapsed/refractory acute lymphoblastic leukemia [ Time Frame: Up to 6 years ]Overall response is defined as complete response (CR) + complete response with hematologic improvement (CRi) in participants with relapsed/refractory disease.
- Complete cytogenetic response [ Time Frame: Up to 6 years ]Will be estimated along with the 95% credible intervals.
- CMR for relapsed/refractory population [ Time Frame: Up to 6 years ]Will be estimated along with the 95% credible intervals.
- Event-free survival (EFS) [ Time Frame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years ]The Kaplan-Meier method will be used to assess EFS probabilities for each cohort.
- Overall survival (OS) [ Time Frame: From the first day of treatment to time of death from any cause, assessed up to 6 years ]The Kaplan-Meier method will be used to assess OS probabilities for each cohort.
- Incidence of adverse events (AEs) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 [ Time Frame: Up to 6 years ]The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.
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): NCT03147612
|Contact: Elias Jabbouremail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Elias Jabbour 713-792-4764|
|Principal Investigator: Elias Jabbour|
|Principal Investigator:||Elias Jabbour||M.D. Anderson Cancer Center|