Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma

The purpose of this study is to evaluate the effectiveness and side effects of the bortezomib, lenalidomide and dexamethasone combination in relapsed or relapsed and refractory multiple myeloma. Each of these drugs are approved by the U.S Food and Drug Administration, but have not been approved in the combination for treating patients in this setting.

• Participants will begin taking the study medication in the clinic on Cycle 1 day 1. Each treatment cycle lasts three weeks. They will take the lenalidomide (capsules) every day for the first two weeks only (days 1-14). They will take dexamethasone (tablets) on Day 1, 2, 4, 5, 8, 9, 11 and 12 and will come to the outpatient treatment center for intravenous bortezomib on Day 1, 4, 8 and 11. The third week of the cycle is a rest period and the participant will not be taking any study medication.
• Certain tests and procedures will be performed throughout each treatment cycle at definitive time periods. These tests include: medical history update, physical/neurological examination, skeletal survey (x-rays or scan), blood samples, urine samples, optional bone marrow aspiration/tissue biopsy, 12-lead ECG, and MRI/CT (if needed).
• It is expected that participants will complete at least 8 cycles of the study, which adds up to 168 days. If the participant completes the first 8 cycles, has stable or responding disease and has not experienced bad side effects, they will be allowed to continue treatment on a maintenance schedule, detailed in the protocol, at the study doctor's discretion.

• Drug: Bortezomib
  Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.
• Drug: Lenalidomide
  Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles
• Drug: Dexamethasone
  Taken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles

Inclusion Criteria:

• Diagnosis of multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria
• Relapsed or relapsed and refractory disease after receiving between 1 and 3 prior regimens
• Negative serum or urine pregnancy test
• Age 18 years or older
• Karnofsky performance status of 60 or greater

Exclusion Criteria:

• Grade 2 or greater peripheral neuropathy within 14 days before enrollment
• Renal insufficiency (serum creatinine > 2.5 mg/dL)
• Evidence of mucosal or internal bleeding and/or platelet refractory
• ANC < 1000 cells/mm3
• Hemoglobin < 8.0 g/dL
• AST or ALT greater than or equal to 2 x ULN
• Concomitant therapy medications that include corticosteroids
• Myocardial infarction within 6 months prior to enrollment of has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Clinically relevant active infection or serious co-morbid medical conditions
• Prior malignancy (within last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, in situ prostate cancer
• Pregnant or breast-feeding
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled diabetes mellitus
• Hypersensitivity to acyclovir or similar anti-viral drug
• POEMS syndrome
• Known HIV infection
• Known active hepatitis B or C viral infection
• Known intolerance to steroid therapy
• Subjects with primary refractory disease, defined as progression during initial treatment

• Brigham and Women's Hospital
• Massachusetts General Hospital
• Celgene Corporation
• Millennium Pharmaceuticals, Inc.