RATIONALE: Radiation therapy using holmium Ho 166 DOTMP may damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy using holmium Ho 166 DOTMP plus melphalan and peripheral stem cell transplantation in treating patients who have multiple myeloma.

Condition	Treatment or Intervention	Phase
stage II multiple myeloma stage III multiple myeloma stage I multiple myeloma refractory plasma cell neoplasm	Drug: holmium Ho 166 DOTMP  Drug: melphalan	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of targeted radiotherapy using holmium Ho 166 DOTMP when combined with melphalan and autologous or syngeneic peripheral blood stem cell transplantation in patients with multiple myeloma. II. Determine the response rate and time to progression in patients treated with this regimen.

PROTOCOL OUTLINE: This is a dose escalation, multicenter study of targeted radiotherapy using holmium Ho 166 DOTMP.

Phase I: Autologous or syngeneic peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. Patients receive an initial test dose of holmium Ho 166 DOTMP IV. Patients with adequate skeletal uptake of the test dose then receive therapeutic dose holmium Ho 166 DOTMP IV over 5-10 minutes for 1-3 days beginning 2 days after test dose infusion and melphalan IV over 20-30 minutes on day -3. PBSC are reinfused beginning a minimum of 24 hours after melphalan infusion and after ongoing radiation to bone marrow falls to less than 1 rad/hour.

Cohorts of 4-7 patients receive escalating doses of targeted radiotherapy using holmium Ho 166 DOTMP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 7 patients experience dose limiting toxicity.

Phase II: Patients receive holmium Ho 166 DOTMP at the MTD from phase I of the study.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Multiple myeloma with one of the following: Complete or partial response to initial chemotherapy OR Primary refractory disease OR Chemotherapy responsive relapse
• Undergoing autologous or syngeneic peripheral blood stem cell transplantation
• No myeloma in refractory relapse

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Prior external beam radiotherapy not to exceed 30 Gy to spinal cord or greater than 20% of bone marrow volume
• Surgery: Not specified
• Other: At least 1 month since prior bisphosphonates; No other concurrent experimental agents

--Patient Characteristics--

• Age: 18 to physiologic 65
• Performance status: Zubrod 0-2
• Life expectancy: Not severely limited by concurrent illness
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 2 mg/dL; SGPT less than 4 times normal
• Renal: Creatinine clearance at least 30 mL/min
• Cardiovascular: No uncontrolled arrhythmias or symptomatic cardiac disease
• Pulmonary: No symptomatic pulmonary disease FEV1, FVC, and DLCO at least 50% of predicted
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; HIV negative; No spinal cord compression

Florida
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States
      University of Washington School of Medicine, Seattle,  Washington,  98195,  United States

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000067396; FHCRC-1442.00; NCI-G99-1623; NEORX-9804
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004158
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08