ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma
Status:
Terminated
Trial end date:
2019-05-01
Target enrollment:
Participant gender:
Summary
This is a Phase Ib/II safety and efficacy trial of single agent ABC294640, an inhibitor of
sphingosine kinase 2 and dihydroceramide desaturase, in refractory or relapsed multiple
myeloma (MM). Cohorts of patients with refractory or relapsed MM who have previously been
treated with proteasome inhibitors and immunomodulatory agents will receive increasing doses
of oral ABC294640. The starting dosage for ABC294640 will be 250 mg bis in die (BID) which is
known to be safely tolerated as a single agent, and the ABC294640 dose will be escalated to
two additional dose cohorts of 500 and 750 mg BID using Bayesian model average continual
reassessment method (BMA-CRM) for dose finding. It is expected that 18 patients will be used
to determine the maximum tolerated dose (MTD) for ABC294640 in refractory or relapsed MM. Up
to 56 additional patients will be treated on the phase II portion of the study at the MTD or
maximum dose used in phase I, with interim stopping rules for futility.
Pharmacokinetic (PK) and pharmacodynamic (PD) assessments of ABC294640 will be conducted on
Day 1 of Cycle 1. Bone marrow biopsy will be obtained prior to the initiation of ABC294640,
at the end of cycle #3 and at the end of cycle #6. In addition to serum protein
electrophoresis (SPEP), urine protein electrophoresis (UPEP) and serum free light chain
measurement, correlative studies will be performed to measure sphingosine kinase 2 (SK2)
activity, sphingosine metabolites, and additional biomarkers in CD138+ myeloma cells.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
RedHill Biopharma Limited
Collaborators:
Apogee Biotechnology Corporation Duke University National Cancer Institute (NCI)