Melphalan and Amifostine Followed By One or Two Autologous or Syngeneic Stem Cell Transplants and Maintenance Therapy in Treating Patients With Stage II-III Multiple Myeloma

PRIMARY OBJECTIVES:

I. Compare the complete response (CR) and near CR rate in patients undergoing autologous stem cell transplant (ASCT) using melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

SECONDARY OBJECTIVES:

I. Compare toxicities between patients receiving amifostine and melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

INDUCTION THERAPY:

ARM I (HIGH DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine intravenously (IV) over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

ARM II (LOW DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Inclusion criteria

• Patients who have MM undergoing autologous or syngeneic hematopoietic transplantation
• Patients must meet Salmon and Durie criteria for initial diagnosis of MM
• Transplant will be offered to patients with stage II or III MM
• Measurable disease, defined as serum monoclonal protein >= 0.2 g/dl or Bence Jones protein >= 200 mg/24 h
• Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2
• Life expectancy is not severely limited by concomitant illness
• Left ventricular ejection fraction >= 50%
• No uncontrolled arrhythmias or symptomatic cardiac disease
• Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO) >= 50%
• No symptomatic pulmonary disease
• Human immunodeficiency virus (HIV) negative
• Bilirubin < 2 mg/dl
• Serum glutamic pyruvate transaminase (SGPT) < 2.5 x normal
• Creatinine clearance >= 60 cc/min, estimated or measured
• Signed informed consent

Exclusion criteria

• Pregnant or lactating females
• Uncontrolled infection
• Planned tandem autologous/reduced intensity allograft
• Insufficient PBSC for an autologous transplant (< 3.0 x 10^6 CD34+ cells/kg total)
• Prior autologous transplant
• Non-secretory myeloma and patients who are in a complete response or near complete response after conventional therapy
• Patients unwilling to practice adequate forms of contraception if clinically indicated
• Male patients on study need to be consulted to use latex condoms, even if they have had a vasectomy, every time they have sex with a woman who is able to have children
• Patients with history of seizures
• Patients receiving antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment