Radiation Therapy Using Holmium Ho 166 DOTMP Plus Melphalan and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Radiation: holmium Ho 166 DOTMP; Procedure: peripheral blood stem cell transplantation; Drug: melphalan

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004158

NEORX-9804

CDR0000067396 (Registry Identifier)

1442.00

NCI-G99-1623

FHCRC-1442.00

Details and patient eligibility

About

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.

Full description

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.

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.

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

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