Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT00568880|
Recruitment Status : Unknown
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was: Recruiting
First Posted : December 6, 2007
Last Update Posted : July 8, 2009
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma and Plasma Cell Neoplasm||Drug: bortezomib Drug: hydroxychloroquine Other: immunologic technique Other: laboratory biomarker analysis Other: mass spectrometry Other: pharmacological study Procedure: biopsy||Phase 1 Phase 2|
- 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 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma|
|Study Start Date :||November 2007|
|Estimated Primary Completion Date :||November 2009|
U.S. FDA Resources
- Dose-limiting toxicity
- Maximum tolerated dose of hydroxychloroquine
- Myeloma response (stringent complete response [sCR], CR, very good partial response [VGPR], PR, stable disease, and progressive disease)
- Overall survival
- Time to treatment failure
- Progression-free survival
- Time to response
- Duration of overall response
- Correlation of hydroxychloroquine and its metabolites blood levels with efficacy by mass spectrometry
- Pre- and post-bortezomib proteasome inhibition assays
- Bone marrow aspirate and peripheral blood mononuclear cell analysis for aggresome formation, autophagy inhibition, and apoptosis
- Rate of overall adverse events and serious adverse events
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): NCT00568880
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Contact: Clinical Trials Office - Abramson Cancer Center of the Univers 800-474-9892|
|Study Chair:||Dan Vogl, MD||Abramson Cancer Center of the University of Pennsylvania|