Ixazomib, ONC201, and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Status:
Terminated
Trial end date:
2020-01-14
Target enrollment:
Participant gender:
Summary
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.