Ixazomib, ONC201, and Dexamethasone in Relapsed/Refractory Multiple Myeloma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03492138|
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : March 22, 2019
ONC201 is a novel dopamine receptor D2 antagonist that is able to activate the integrated stress response pathway. It is active against multiple myeloma cells in vitro, both as a single agent and in combination with corticosteroids and proteasome inhibitors. In order to document superiority over the combination compared to the individual agents of ixazomib and ONC201 in a single arm study, there will initially be a run-in period of weekly ONC201 625 mg with dexamethasone 40 mg such that if there is progression of disease (25% increase) after 4 weeks or less than a minimal response (25% reduction) after 8 weeks then ixazomib will be added. Dexamethasone is dose-reduced to 20 mg at the same schedule for subjects ≥ 75 years old. If patients do achieve single-agent responses with ONC201 (minimal response or better), they will continue with weekly ONC201 and dexamethasone until progression, with response assessments after each 28-day cycle. Patients who have previously been treated on another clinical trial with weekly ONC201 625mg with dexamethasone with progression while receiving treatment do not need to complete the run-in phase of the study.
At the time of progression, they will proceed to the 3 drug combination phase of the study. It is at the point of 3 drug initiation, that below phase I DLT principles or phase II disease control rate considerations apply.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: ONC201 Drug: Ixazomib Drug: Dexamethasone||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single arm, open-label, standard 3+3 phase 1 with a Simon 2-stage design followed by stage 2|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of the Addition of Ixazomib to ONC201 and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma|
|Actual Study Start Date :||March 26, 2018|
|Estimated Primary Completion Date :||March 15, 2023|
|Estimated Study Completion Date :||March 15, 2023|
Experimental: Participants with relapsed/refractory multiple myeloma
ONC201, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma. Run-in phase of ONC201 and dexamethasone weekly until progression at 4 weeks, lack of response at 8 weeks, or progression followed by the addition of weekly ixazomib.
Dose to be determined in Phase 1 of study
- Recommended phase II dose (RPTD) [ Time Frame: 9 Months ]of triplet therapy (ixazomib + ONC201+ dexamethasone) following a 3+3 escalation design
- Disease control rate [ Time Frame: 2 months ]2 month disease control rate defined as the proportion of patients that have stable or better disease after two months of treatment initiation according to IMWG criteria: Stable disease, partial remission, or complete remission
- Progression free survival (PFS) [ Time Frame: 6 months ]Median Progression free survival for the phase I and II patients treated at the recommended phase II dose. PFS is defined as the duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier.
- Duration of response (DOR) [ Time Frame: 6 months ]Median duration of response for the phase I and II patients treated at the recommended phase II dose. DOR is defined as the time from first evidence of PR or better to confirmation of disease progression.
- Clinical benefit rate (CBR) [ Time Frame: 6 months ]Clinical benefit rate for the phase I and II patients treated at the recommended phase II dose level. CBR is the combination of the ORR and minimal response (MR) i.e. this includes sCR, CR, VGPR, PR, and MR.
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): NCT03492138
|Contact: Lisa La, MS||212-241-7873||Lisa.La@mssm.edu|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Lisa La, MS 212-241-7873 Lisa.La@mssm.edu|
|Principal Investigator:||Ajai Chari, MD||Icahn School of Medicine at Mount Sinai|