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 : September 10, 2021
|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|
I. To evaluate the maximum-tolerated dose (MTD) and assess the safety 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 patient bone marrow (or peripheral blood) before and after treatment with the ruxolitinib and venetoclax combination.
II. To use molecular techniques (potentially including next-generation sequencing and/or BH3 profiling) to examine the mechanisms of response versus (vs.) no response.
III. To correlate molecular features with the patient response and resistance to venetoclax combination therapies.
IV. To determine the pharmacokinetic/pharmacodynamic (PK/PD) concentrations in vivo of the dual drug combination therapy.
OUTLINE: This is a dose-escalation study of ruxolitinib.
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 the discretion of the sponsor-investigator.
After completion of study treatment, patients are followed up every 6 months.
|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, 2022|
|Estimated Study Completion Date :||December 31, 2023|
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 the discretion of the sponsor-investigator.
- Dose-limiting toxicities (DLT) of ruxolitinib and venetoclax in combination [ Time Frame: Up to day 56 ]The maximum-tolerated dose (MTD) of ruxolitinib and venetoclax combination will be determined according to the "keyboard" Bayesian toxicity probability interval design. The MTD of the ruxolitinib and venetoclax combination will correspond to the dose level closest to the target DLT probability of 30% and will be estimated from observed dose level-specific DLT rates using isotonic regression. The study will start at dose level 0 with a potential escalation/de-escalation decision occurring for each subsequent cohort of 3 enrolled participants according to the predefined keyboard rules until a dose level has been assigned to all 30 subjects.
- Composite complete remission rate [ Time Frame: From first dose to end of cycle 2 (up to 36 days) ]Will be estimated, along with 95% confidence intervals.
- Clinical benefit rate (CBR) [ Time Frame: From first dose to end of cycle 2 (up to 36 days) ]The clinical benefit rate (CBR) is defined as the proportion of evaluable subjects obtaining stable disease (SD), partial remission (PR), or composite complete remission (CCR) during the first 2 cycles of therapy. Will be estimated, along with 95% confidence intervals.
- Event-free survival [ Time Frame: From first dose to end of treatment, relapse from >= partial response (PR), disease progression, or death (whichever occurs first), or date of last exam, assessed up to 12 months ]Kaplan-Meier method will be used to estimate and plot event-free survival.
- Overall survival [ Time Frame: From date of first dose to death or date of last known alive, assessed up to 12 months ]Kaplan-Meier method will be used to estimate and plot overall survival.
- Overall incidence of treatment-related and non-treatment related toxicity [ Time Frame: From first dose to 30 days after last dose of study agent ]The overall incidence of treatment- related and non-treatment- related toxicity will be determined using the safety-evaluable population. The point estimate and 95% confidence interval for the proportion of patients with each of these toxicity types will be reported. Each toxicity event (there can be > 1 event per participant) will be tabulated by dose level and summarized by severity and major organ site according to the Common Terminology Criteria for Adverse Events version 5.0.
- Duration of response [ Time Frame: From first PR or better to loss of best response, or date of last assessment (up to 24 months) ]Cumulative incidence functions will be applied to the "competing risks" of the duration of response endpoint, namely, loss of best response and non-relapse death.
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
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Jennifer N. Saultz, MD 503-494-5566 email@example.com|
|Principal Investigator: Jennifer N. Saultz, MD|
|United States, Texas|
|UT Southwestern/Simmons Cancer Center-Dallas||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Payal Dixit, MD 214-648-7097 firstname.lastname@example.org|
|Principal Investigator: Prapti Patel, MD|
|Principal Investigator:||Jennifer Saultz, MD||OHSU Knight Cancer Institute|