Ruxolitinib in Combination With Venetoclax for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03874052|
Recruitment Status : Not yet recruiting
First Posted : March 14, 2019
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Acute Myeloid Leukemia, in Relapse||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.
The study will start at dose level 0 and the dose is escalated/de-escalated according to the Bayesian Optimal Interval Design (BOIN) rule in a cohort of 3 participants until the total of 30 participants are evaluated or the maximum of 15 patients at one dose level. The rule is based on a target dose limiting toxicity (DLT) of 0.30. Participants, on Day 1, will receive a starting dose (i.e., dose level 0) of ruxolitinib (20 mg PO, b.i.d) and venetoclax (200 mg, PO, qd). Per BOIN, a cohort of 3 participants will be treated at the same dose level, or higher or lower dose level, depending on the cumulative number of participants experiencing DLT and number of individuals treated at that dose level.
Participants will be followed in subsequent cycles for safety and will be assessed for status of their disease in every second cycle or as otherwise specified. Treatment cycles will be repeated until intolerability or disease progression.
|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|
|Estimated Study Start Date :||March 15, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Combination Ruxolitinib and Venetoclax
Participants, on Day 1, will receive a starting dose (i.e., dose level 0) of ruxolitinib (20 mg PO, b.i.d) and venetoclax (200 mg, PO, qd). A cohort of 3 participants will be treated at the same dose level, or higher or lower dose level, depending on the cumulative number of participants experiencing DLT and number of individuals treated at that dose level. Treatment cycles will be repeated until intolerability or disease progression.
Administered orally (PO), twice daily at assigned dose levels ranging from 5 mg - 50mg.
Administered orally (PO), twice daily at assigned dose levels ranging from 100 mg - 600mg.
- DLT of Ruxolitinib and Venetoclax in combination. [ Time Frame: Up to Day 28 ]The 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: Tara Maceyemail@example.com|
|United States, Oregon|
|OHSU Knight Cancer Institute||Not yet recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Tara Macey firstname.lastname@example.org|
|Principal Investigator: Uma Borate, MD|
|Principal Investigator:||Uma Borate, MD||OHSU Knight Cancer Institute|