RATIONALE: PS-341 may stop the growth of cancer cells by blocking the enzymes necessary for
cancer cell growth. It is not yet known if PS-341 is effective in treating patients who have
PURPOSE: Randomized phase III trial to study the effectiveness of PS-341 in treating
patients who have refractory or progressive multiple myeloma.
- Determine the time to progressive disease in patients with refractory or progressive
multiple myeloma treated with PS-341.
- Determine the safety and tolerability of this drug in these patients.
- Determine survival of patients treated with this drug.
- Determine the rate and duration of response (complete and partial) in patients treated
with this drug.
- Assess the relationship between selected genetic disease markers and response in
patients treated with this drug.
OUTLINE: This is an open-label, multicenter study.
- Induction therapy: Patients receive PS-341 IV on days 1, 4, 8, and 11. Treatment
repeats every 3 weeks for up to 8 courses.
- Maintenance therapy: Patients receive PS-341 IV on days 1, 8, 15, and 22. Treatment
repeats every 5 weeks for up to 3 courses.
Patients who experience progressive disease (PD) after at least 2 courses or no change after
at least 4 courses may also receive oral dexamethasone on the day of and the day after
PS-341 administration. Patients who experience PD after at least 2 courses of this combined
therapy go off study.
Patients are followed at 30 days, every 6 weeks until disease progression, and then every 3
PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 1 year.
- Diagnosis of multiple myeloma (MM) and meeting 1 of the following criteria:
- Progressive disease during or after treatment with high-dose dexamethasone on
MPI Study M34101-039 (FHCRC-1746.00), with no other antineoplastic treatment for
- Relapsed or progressive disease after receiving at least 4 prior treatment
regimens for MM (non-MPI patients)
- Karnofsky 60-100% (non-MPI patients)
- Not specified
- Absolute neutrophil count at least 500/mm^3 (no growth factor support)
- Platelet count at least 20,000/mm^3 (transfusions allowed)
- Hemoglobin at least 7.0 g/dL (transfusions allowed)
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST and ALT no greater than 2.5 times ULN
- Hepatitis B surface antigen negative
- No known active hepatitis C infection
- Calcium less than 14 mg/dL
- Creatinine clearance at least 20 mL/min
- Non-MPI patients:
- No myocardial infarction within the past 6 months
- No New York Heart Association class III or IV heart failure
- No uncontrolled angina
- No severe uncontrolled ventricular arrhythmias
- No acute ischemia or active conduction system abnormalities by EKG
- No cardiac amyloidosis
- No poorly controlled hypertension
- All patients:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Non-MPI patients:
- No other serious medical or psychiatric illness that would preclude study
- No prior allergic reaction attributable to compounds containing boron or
- No peripheral neuropathy grade 2 or greater
- No diabetes mellitus
- No active systemic infection requiring treatment
- MPI patients:
- Recovered from dexamethasone-related toxicity
- No other new or worsening existing illness that would preclude study
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior immunotherapy or antibody therapy (non-MPI patients)
- No concurrent thalidomide
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) (non-MPI
- See Disease Characteristics
- At least 3 weeks since prior corticosteroids (greater than 10 mg/day of prednisone or
equivalent) (non-MPI patients)
- No other concurrent corticosteroids (e.g., greater than 10 mg/day of prednisone or
- Concurrent local short-duration radiotherapy allowed
- At least 4 weeks since prior major surgery (except kyphoplasty) (non-MPI patients)
- Concurrent kyphoplasty allowed
- Concurrent emergency orthopedic procedures allowed
- No other concurrent antineoplastic treatment for MM
- No other concurrent investigational agents, including commercial agents approved for
other indications but investigational for MM
- No concurrent clarithromycin
- Concurrent bisphosphonates allowed