Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

• Status: Completed
• Trial end date: 2011-06-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abramson Cancer Center of the University of Pennsylvania; University of Pennsylvania
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bortezomib; Hydroxychloroquine

Criteria

Inclusion criteria:

• Histologically confirmed multiple myeloma

• Documented relapse or continued disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)

• Need for further therapy for myeloma, as determined by the patient's treating physician

• Age greater than 18 years

Exclusion Criteria

• Baseline peripheral neuropathy of grade 2 or higher

• History of allergic reactions to compounds of similar chemical or biologic composition to bortezomib or hydroxychloroquine

• Prior dose-limiting toxicity with bortezomib

• Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis. Patients with well-controlled psoriasis may participate in the study provided that they are under the care of a specialist in this condition who agrees to monitor the patient for exacerbations.

• Other conditions that would require therapy with hydroxychloroquine, including but not limited to systemic lupus, rheumatoid arthritis, porphyria cutanea tarda, and malaria treatment or prophylaxis

• ECOG performance status >2 (for definition, see section 0)

• Life expectancy of less than 3 months

• Lack of adequate organ or bone marrow function based on lab values drawn ≤ 14 days before beginning treatment.

• Concurrent treatment with a different investigational regimen. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.

• Treatment with other anti-myeloma agents, including thalidomide or lenalidomide, within the 14 days prior to initiating hydroxychloroquine. Treatment with corticosteroids will be permitted up to 7 days prior to initiating hydroxychloroquine. Corticosteroids that are being used for other diseases are permitted if the dose is less than the equivalent of 20 mg of prednisone daily. Concurrent therapy with bisphosphonates through the study period is permitted at the discretion of the treating physician. Concurrent hematopoietic growth factors are also permitted, including filgrastim or pegfilgrastim, epoetin alpha, and darbepoetin alpha

• Known central nervous system involvement. The poor prognosis and progressive neurological dysfunction associated with central nervous system involvement would confound the evaluation of neurological and other adverse events. The presence of calvarial lytic lesions or plasmacytomas is not an exclusion criterion if there is no central nervous system involvement.

• Concurrent malignancy other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, any carcinoma in situ, or localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a period of at least 4 months. Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy ≥4 years previously with no evidence of recurrent disease. Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy ≥2 years previously with no evidence of recurrent disease.

• Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Inability to understand the informed consent document or unwillingness to consent. Written informed consent must be obtained from all patients before study entry.

• Pregnancy or breastfeeding.

• Unwillingness to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation for men and women of child-bearing potential.