Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to
      stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Giving hydroxychloroquine together with bortezomib may kill more
      cancer cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of
      hydroxychloroquine when given together with bortezomib and to see how well it works in
      treating patients with relapsed or refractory multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  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.

      Secondary

        -  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 II
      study.

        -  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.
    

Intervention name(s): bortezomib; hydroxychloroquine
Intervention type(s): Drug; Drug
Intervention description(s): bortezomib 1.0-1.3mg/m2 IV; hydroxychloroquine 200 mg pill
Other intervention name(s): Velcade; Plaquenil
Intervention MeSH terms: Hydroxychloroquine; Bortezomib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma