A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma
- To establish the dose-limiting toxicities and maximum tolerated dose of
hydroxychloroquine when added to a standard-dose regimen of bortezomib for treatment of
patients with relapsed or refractory multiple myeloma.
- To obtain a preliminary estimate of the toxicity rate and response rate of this
combination at the maximum tolerated dose.
- To confirm preclinical evidence showing synergistic effects of hydroxychloroquine and
bortezomib by correlating response rate with blood levels of hydroxychloroquine and
degree of autophagy inhibition in repeated bone marrow samples.
OUTLINE: This is a phase I dose-escalation study of hydroxychloroquine followed by a phase
- Phase I: Patients receive oral hydroxychloroquine every other day for 2 weeks. Patients
then receive oral hydroxychloroquine 1-3 times daily or every other day and bortezomib
IV twice a week for 2 weeks. Treatment with hydroxychloroquine and bortezomib repeats
every 3 weeks for at least 2 courses in the absence of disease progression or
unacceptable toxicity. Once the maximum tolerated dose (MTD) for hydroxychloroquine is
determined, additional patients are accrued to the phase II portion of the study.
- Phase II: Patients receive hydroxychloroquine (at the MTD determined in phase I) and
bortezomib as in phase I.
Blood and bone marrow samples are collected periodically during the study for correlative
studies by mass spectrometry, proteasome inhibition assays, pharmacokinetic analysis and
assessment of aggresome formation, autophagy inhibition, and apoptosis by protein
electrophoresis and serum free light-chain analysis.
After completion of study treatment, patients are followed periodically.
Masking: Open Label, Primary Purpose: Treatment
Dan Vogl, MD
Abramson Cancer Center of the University of Pennsylvania
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|