Patient Abstract available in the near future.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma	Drug: filgrastim  Drug: holmium Ho 166 DOTMP  Drug: melphalan	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the efficacy of melphalan with or without holmium Ho 166 DOTMP followed by autologous peripheral blood stem cell transplantation in patients with multiple myeloma. II. Compare the response rate and overall survival of these patients treated with these regimens. III. Compare the hematologic recovery rate and time to granulocyte engraftment of these patients treated with these regimens. IV. Compare the toxicity of these regimens in this patient population.

PROTOCOL OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to their beta 2 microglobulin (B2M) test at initial diagnosis (B2M no greater than 4 mg/L vs B2M greater than 4 mg/L vs unknown B2M). Patients are randomized to one of two treatment arms. Prior to stratification and randomization, patients receive a diagnostic dose of holmium Ho 166 DOTMP within days -31 to -10. Patients with adequate skeletal uptake of the diagnostic dose are randomized for therapy. Arm I: Patients receive holmium Ho 166 DOTMP IV over no more than 10 minutes within days -10 to -7 (at least 1 week and no more than 3 weeks after the diagnostic dose), melphalan IV over 20-30 minutes within days -3 to -1 (at least 24 hours prior to autologous peripheral blood stem cell (PBSC) transplantation), and autologous PBSC transplantation on day 0. Arm II: Patients receive melphalan and autologous PBSC transplantation as in arm I. Following transplantation, patients receive filgrastim (G-CSF) daily until blood counts recover. Patients are followed at 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 300 patients (150 per treatment arm) will be accrued for this study within 9 months.

Ages Eligible for Study:  18 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Newly diagnosed multiple myeloma (diagnosis within 12 months of study) and scheduled to undergo autologous peripheral blood stem cell transplantation; Prior diagnosis of monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM) allowed if the criteria for diagnosis of multiple myeloma was met within 12 months of study
• Serum or urinary M-protein confirmation of diagnosis (IgA, IgD, IgG, IgE, or light chain proteins)
• At least 10% plasma cells in bone marrow
• Must have received induction therapy without disease progression or relapse after initial response
• Prior induction therapy must have been completed no more than 6 months before stem cell collection and no more than 9 months before transplantation
• Must have undergone stem cell mobilization with cyclophosphamide IV and filgrastim (G-CSF)
• The following diagnoses are excluded: Non-secretory multiple myeloma IgM myeloma; Solitary bone or extramedullary plasmacytoma; Symptomatic MGUS or SMM; Symptomatic indolent multiple myeloma

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; No prior thalidomide for myeloma No prior peripheral blood stem cell or bone marrow transplantation; No concurrent thalidomide; No concurrent interferon
• Chemotherapy: See Disease Characteristics; No prior clarithromycin for myeloma; No more than 2 courses of prior induction therapy containing an alkylating agent
• Endocrine therapy: No concurrent dexamethasone
• Radiotherapy: No prior radiotherapy to more than 20% of bone marrow; No greater than 30 Gy to the spinal cord
• Surgery: Not specified
• Other: At least 28 days since prior bisphosphonates; No prior new or experimental agents for myeloma; No concurrent experimental therapies; No concurrent bisphosphonates

--Patient Characteristics--

• Age: 18 to 70
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Bilirubin no greater than 2 mg/dL; SGPT no greater than 2 times upper limit of normal; No clinical evidence of amyloidosis involving the liver
• Renal: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 30 mL/min; No clinical evidence of amyloidosis involving the kidney
• Cardiovascular: LVEF at least 50% No evidence of amyloidosis on echocardiogram; No uncontrolled arrhythmia; No symptomatic cardiac disease
• Pulmonary: FEV1 at least 60% OR FVC at least 60% OR DLCO at least 60%; No symptomatic pulmonary disease; No clinical evidence of amyloidosis involving the lungs
• Other: HIV negative; No cord compression; No other concurrent illness that would preclude survival; No clinical evidence of amyloidosis involving the autonomic nervous system or gastrointestinal tract; No known allergy to vitamin C; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

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

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000068389; FHCRC-1542.00; NCI-G00-1892
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008229
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08