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 multiple myeloma.

PURPOSE: Randomized phase III trial to study the effectiveness of PS-341 in treating patients who have refractory or progressive multiple myeloma.

Condition	Treatment or Intervention	Phase
refractory plasma cell neoplasm	Drug: bortezomib  Drug: dexamethasone  Procedure: endocrine therapy  Procedure: enzyme inhibitor therapy  Procedure: hormone therapy  Procedure: steroid therapy	Phase III

Further Study Details: 

OBJECTIVES:

• 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.
• 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 months thereafter.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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 MM initiated
• Relapsed or progressive disease after receiving at least 4 prior treatment regimens for MM (non-MPI patients)

PATIENT CHARACTERISTICS: Age

• Adult

Performance status

• Karnofsky 60-100% (non-MPI patients)

Life expectancy

• Not specified

Hematopoietic

• 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)

Hepatic

• 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

Renal

• Calcium less than 14 mg/dL
• Creatinine clearance at least 20 mL/min

Cardiovascular

• 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

Other

• 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 mannitol
• 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: Biologic therapy

• At least 4 weeks since prior immunotherapy or antibody therapy (non-MPI patients)
• No concurrent thalidomide

Chemotherapy

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) (non-MPI patients)

Endocrine therapy

• 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 equivalent)

Radiotherapy

• Concurrent local short-duration radiotherapy allowed

Surgery

• At least 4 weeks since prior major surgery (except kyphoplasty) (non-MPI patients)
• Concurrent kyphoplasty allowed
• Concurrent emergency orthopedic procedures allowed

Other

• 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

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States

Study chairs or principal investigators

William I. Bensinger, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000258110; FHCRC-1747.00; MILLENNIUM-M34101-040; NCI-G02-2128
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049478
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08