High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse
High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.
 Combining peripheral stem cell transplantation with chemotherapy and radiation therapy may
 allow the doctor to give higher doses of radiation and chemotherapy drugs and kill more tumor
 cells.

 PURPOSE: Phase II trial to study the effectiveness of high-dose melphalan plus total-body
 irradiation and peripheral stem cell transplantation in treating patients with multiple
 myeloma in first relapse.
OBJECTIVES: I. Assess bone marrow reconstitution and peripheral blood cell counts of patients
 with multiple myeloma treated with high-dose melphalan (L-PAM) and total-body irradiation
 (TBI) followed by peripheral blood stem cell (PBSC) rescue. II. Assess the efficacy of
 intravenous L-PAM and TBI for treatment of relapsing/refractory myeloma. III. Assess the
 tolerability and toxicity of this regimen in patients with relapsing multiple myeloma. IV.
 Assess response rate and survival of relapsing/refractory patients treated with this regimen.

 OUTLINE: Prior to entry, patients will have received 3 monthly courses of standard VAD
 followed by PBSC collection on Regimen A; those who responded to VAD continue standard VAD to
 best response and upon relapse (on or off therapy) proceed to Regimen B. Patients with no
 response to 3 courses of VAD and those with no response to an alkylating-based regimen
 proceed immediately to Regimen B following PBSC collection. The following acronyms are used:
 CTX Cyclophosphamide, NSC-26271 G-CSF Granulocyte Colony Stimulating Factor (Amgen),
 NSC-614629 L-PAM Melphalan, NSC-8806 PBSC Peripheral Blood Stem Cells VAD
 Vincristine/Doxorubicin/Dexamethasone TBI Total Body Irradiation Regimen A: Stem Cell
 Mobilization/Harvest. CTX; G-CSF. Regimen B: Single-Agent Myeloablative Chemoradiotherapy
 with Stem Cell Rescue. L-PAM; TBI (Co60 or linear accelerators of 4 MV or greater); with
 PBSC.

 PROJECTED ACCRUAL: If 9 or fewer or 20 or more responses are seen in the first 50 patients
 treated, the study will be discontinued.
DISEASE CHARACTERISTICS: Multiple myeloma confirmed by bone marrow plasmacytosis and with
 measurable M-component in the serum or urine by immunoelectrophoresis or immunofixation No
 Stage I myeloma No smoldering multiple myeloma Refractory to or in first relapse following
 an initial response to VAD (vincristine/doxorubicin/dexamethasone), with relapse defined as
 any of the following: 50% increase above the lowest remission level of serum or urine
 M-protein while on therapy 25-50% increase above the lowest remission level of serum or
 urine M-protein associated with either: Hypercalcemia (greater than 11 mg/dl) Hb decrease
 of 2 g/dl attributable to increasing marrow plasmacytosis Appearance of new lytic lesions
 Calcium no greater than 11 mg/dl No myeloma meningitis No plasma cell leukemia

 PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: ECOG 0-2 Hematopoietic: WBC
 greater than 500 (after G-CSF) Platelets greater than 25,000 Hepatic: Bilirubin no greater
 than 2.0 mg/dl Renal: Creatinine no greater than 2.0 mg/dl Cardiovascular: No NYHA class
 II-IV disease Pulmonary: DLCO at least 50% of predicted FVC at least 75% of predicted FEV1
 at least 60% of predicted Other: No uncontrolled infection No active fungal infection No
 fever No prior malignancy within 5 years except: Basal cell skin cancer In situ carcinoma
 of the cervix No pregnant or nursing women

 PRIOR CONCURRENT THERAPY: Biologic therapy: Prior biological response modifiers allowed
 Chemotherapy: No time limit between cytotoxic therapy and protocol treatment Prior
 cumulative melphalan dose less than 300 mg Endocrine therapy: Corticosteroids for
 hypercalcemia allowed Radiotherapy: Prior radiotherapy allowed Prior pelvic radiotherapy
 allowed, but patients with such therapy are unlikely to have adequate PBSC harvested
 Surgery: Not specified