Ruxolitinib and Venetoclax in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03874052|
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : October 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Ruxolitinib Drug: Venetoclax||Phase 1|
To evaluate the maximum tolerated dose (MTD) of ruxolitinib in combination with venetoclax.
I. To assess the preliminary efficacy of the ruxolitinib and venetoclax combination.
II. To estimate overall and event-free survival.
I. To assess in vitro kinase inhibitor sensitivity using patients' bone marrow in response to ruxolitinib and venetoclax combination.
II. Use molecular techniques (potentially including next-generation sequencing and/or BH3 profiling) to examine the mechanisms of response vs. no response
III. To correlate molecular features with the patient response and resistance to venetoclax combination therapies.
Patients receive ruxolitinib orally (PO) twice daily (BID) and venetoclax PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of ruxolitinib and venetoclax at physician's discretion.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study to Evaluate Safety of Ruxolitinib in Combination With Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia|
|Actual Study Start Date :||August 16, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Treatment (ruxolitinib, venetoclax)
Patients receive ruxolitinib PO BID and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of ruxolitinib and venetoclax at physician's discretion.
- Dose limiting toxicities (DLT) of ruxolitinib and venetoclax in combination. [ Time Frame: Up to Day 28 ]The maximum tolerated dose (MTD) of ruxolitinib and venetoclax combination will be determined according to the hierarchical Bayesian model of the BOIN design.42 The MTD of ruxolitinib and venetoclax in combination is the dose corresponding to a DLT probability of 30%. The study will start with dose level 0 with escalation/de-escalation of the dose level) occurring in a cohort of 3 participants according to the BOIN rule until a total of 30 participants or the maximum of 15 patients at a dose level are evaluated.
- Composite complete remission rate [ Time Frame: From first dose to Cycle 2 (up to 36 days) ]
- Clinical benefit rate (CBR) [ Time Frame: From first dose to Cycle 2 (up to 36 days) ]The clinical benefit rate (CBR) is defined as the proportion of evaluable subjects obtaining stable disease (SD), PR, or CCR during the first 2 cycles of therapy.
- Overall Survival at 12 months [ Time Frame: From date of first dose to date of death or last contact, whichever came first, assessed up to 12 months ]Kaplan-Meier method will be used to estimate overall survival.
- Overall incidence of treatment-related and non-treatment related toxicity [ Time Frame: From first PR/CR to 30 days after last dose ]Overall incidence of treatment and non-treatment related toxicity will be estimated, and 95% confidence intervals will be provided.
- Duration of response. [ Time Frame: From first PR/CR to 30 days after last dose ]For patients that achieve >= PR, how long do they maintain this response before progression.
- Event-free survival [ Time Frame: From first dose to 24 months post treatment ]Kaplan-Meier method will be used to estimate event-free survival.
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): NCT03874052
|Contact: Madison Hayesemail@example.com|
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Madison Hayes 503-494-3835 firstname.lastname@example.org|
|Principal Investigator: Uma Borate, MD|
|United States, Texas|
|University of Texas Southwestern Medical Center||Not yet recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Prapti Patel|
|Principal Investigator: Prapti Patel|
|Principal Investigator:||Uma Borate, MD||OHSU Knight Cancer Institute|