Melphalan With or Without Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
Melphalan With or Without Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Radioactive drugs such as holmium Ho 166 DOTMP can kill cancer
 cells without harming healthy cells. Peripheral stem cell transplantation may be able to
 replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill
 tumor cells.

 PURPOSE: Randomized phase III trial to compare the effectiveness of melphalan with or without
 holmium Ho 166 DOTMP followed by peripheral stem cell transplantation in treating patients
 who have multiple myeloma.
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.

 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.
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

 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

 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