Decitabine, Venetoclax, and Ponatinib for the Treatment of Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase Chronic Myelogenous Leukemia
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|ClinicalTrials.gov Identifier: NCT04188405|
Recruitment Status : Recruiting
First Posted : December 5, 2019
Last Update Posted : July 15, 2020
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Recurrent Acute Myeloid Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Refractory Acute Myeloid Leukemia Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive||Drug: Decitabine Drug: Ponatinib Drug: Venetoclax||Phase 2|
I. To determine the efficacy of the regimen, as defined by the rate of complete remission (CR) or CR with incomplete count recovery (CRi).
I. To determine efficacy outcomes, including rate of minimal residual disease negativity by flow cytometry and polymerase chain reaction (PCR) for BCR-ABL1 transcripts, median relapse-free survival, and median overall survival.
II. To determine the proportion of patients proceeding to allogeneic stem cell transplant (ASCT).
III. To preliminarily determine the safety of the combination regimen.
I. To evaluate the effect of single-agent ponatinib on apoptotic proteins and Bcl-2 dependency.
II. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen.
Patients recently (within 2 weeks of anticipated start date) treated with ponatinib receive ponatinib orally (PO) daily on days 1-28, venetoclax PO daily on days 1-21, and decitabine intravenously (IV) over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not been recently (within 2 weeks of anticipated start date) treated with ponatinib may receive ponatinib monotherapy PO daily on days 1-7 before starting combination therapy with venetoclax in cycle 1. After completion of ponatinib lead-in, patients will receive ponatinib PO daily on days 1-21 of cycle 1 and on days 1-28 of subsequent cycles, venetoclax PO daily on days 8-28 of cycle 1 and days 1-21 of subsequent cycles, and decitabine IV over 60 minutes on days 8-12 of cycle 1 and days 1-5 of subsequent cycles. For these patients, cycle 1 is 35 days in duration and cycles 2-24 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 then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of the Combination of Decitabine, Venetoclax, and Ponatinib in Patients With Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase Chronic Myelogenous Leukemia|
|Actual Study Start Date :||May 17, 2020|
|Estimated Primary Completion Date :||September 1, 2024|
|Estimated Study Completion Date :||September 1, 2024|
Experimental: Treatment (ponatinib, venetoclax, decitabine)
See Detailed Description.
- Overall response rate [ Time Frame: End of cycle 2 (each cycle is 28 days) ]Defined as the proportion of patients achieving complete remission (CR) + CR with incomplete count recovery (CRi) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.
- Rate of minimal residual disease negativity [ Time Frame: Up to 4.5 years ]Will be estimated along with the 95% credible interval.
- Proportion of patients proceeding to allogeneic stem cell transplant [ Time Frame: Up to 4.5 years ]Will be estimated along with the 95% credible interval.
- Relapse-free survival (RFS) [ Time Frame: From the date of treatment initiation to the date of documented treatment relapses from CR/CRi or death from any cause, whichever occurs first, assessed up to 4.5 years ]The distribution of RFS will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
- Overall survival (OS) [ Time Frame: From treatment start till death or last follow-up, assessed up to 4.5 years ]The distribution of OS will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
- Incidence of adverse events [ Time Frame: Up to 4.5 years ]Safety data will be summarized by category, severity and frequency.
- Apoptotic protein expression and Bcl-2 dependency on response and resistance [ Time Frame: Up to 4.5 years ]The correlation between response and patient's clinical information such as apoptotic protein expression, etc. will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
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): NCT04188405
|Contact: Nicholas Shortfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Nicholas Short 713-563-4485 email@example.com|
|Principal Investigator: Nicholas Short|
|Principal Investigator:||Nicholas Short||M.D. Anderson Cancer Center|