Samarium Sm 153 Lexidronam Pentasodium and High-Dose Melphalan in Treating Patients With Multiple Myeloma Undergoing Stem Cell Transplant

OBJECTIVES:

• To find the maximum tolerated dose of samarium Sm 153 lexidronam pentasodium when given with fixed high-dose melphalan as a conditioning regimen for autologous peripheral blood stem cell transplantation in patients with multiple myeloma. (Phase I)
• To assess the response rates of this regimen in these patients. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of samarium Sm 153 lexidronam pentasodium followed by a phase II study.

• Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV once between days -14 and -10. Patients also receive melphalan IV on day -1. Patients undergo peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover.
• Phase II: Patients receive samarium Sm 153 lexidronam pentasodium at the MTD determined in phase I .

Blood samples are collected periodically to determine clearance of samarium Sm 153 lexidronam pentasodium and bone marrow dosimetry.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma requiring treatment
• Must have at least 2 x 10^6 CD34+ cells collected for peripheral blood stem cell transplantation

PATIENT CHARACTERISTICS:

Inclusion criteria

• ECOG performance status (PS) 0-2 (ECOG PS > 2 allowed if secondary to neuropathy or acute bone event)
• Direct bilirubin ≤ 2.0 mg/dL
• Alkaline phosphatase ≤ 750 μ/L
• Creatinine ≤ 3.0 mg/dL
• Ejection fraction ≥ 45%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 6 months after the completion of study therapy

Exclusion criteria

• DLCO < 50%
• FVC < 50%
• FEV_1 < 50%
• Active malignancy with the exception of nonmelanoma skin cancer
• Uncontrolled infection
• NYHA class III-IV cardiac disease

PRIOR CONCURRENT THERAPY:

• May or may not have received prior chemotherapy
• At least 3 weeks since prior chemotherapy

• Cyclophosphamide pulsing for stem cell collection allowed
• At least 4 weeks since prior biologic therapy
• At least 2 weeks since prior bisphosphonates and bisphosphonates maybe resumed 1 month post-study treatment