Melphalan, Peripheral Stem Cell Transplantation, and Interleukin-2 Followed by Interferon Alfa in Treating Patients With Advanced Multiple Myeloma

PRIMARY OBJECTIVES:

I. Evaluate initial response to therapy, time to disease progression, and overall survival in MM patients treated with melphalan, IL2- incubated peripheral blood stem cells, and sequential IL2.

SECONDARY OBJECTIVES:

I. Evaluate grade 3-4 toxicities encountered by younger (< 56 years old) and older (>56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.

OUTLINE:

Patients receive melphalan intravenously (IV) over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa subcutaneously (SC) 3 times a week in the absence of disease progression or unacceptable toxicity.

Inclusion criteria

• Patient must be less than 70 years old
• Patients with advanced Multiple Myeloma that meet the eligibility requirements for mobilization/debulking with Cytoxan/VP-16/G-CSF, Cytoxan/Taxol/G-CSF, or Cytoxan/G-CSF (according to protocol 506.03); if clinically indicated a lower dose of cytoxan than 4g/m2 may be used for mobilization based on the attending's discretion; also, if the patients had previously collected PBSC of sufficient number in the past and meet the other eligibility requirements, they may be entered on this study after approval by the PI
• Patients with advanced Multiple Myeloma that have an identical syngeneic twin for donation of PBSCs
• Patients have advanced Multiple Myeloma if they were diagnosed initially with stage II or III disease or had stage I disease that progressed after initial therapy or failed to respond to therapy
• Syngeneic Donor Inclusion:

• Donor and patient have adequate documentation that donor and recipient are syngeneic; including ABO typing, HLA typing and VNTR studies
• Donor > 20 kg
• Donor meets eligibility to donate according to Standard Practice Guidelines

Exclusion criteria

• Patient's age >= 70
• Karnofsky score less than 80
• A left ventricular ejection fraction less than 50%; Patients with congestive heart disease, history of myocardial infarction (MI), coronary artery disease or any arrhythmia history
• Total bilirubin > 1.5 mg/ml (unless history of Gilbert's disease)
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2 x upper limit of normal
• Estimated creatinine clearance < 60 ml/min or creatinine serum > 2.0 mg/dl
• Pregnancy
• Seropositivity for human immunodeficiency virus
• Patients who cannot give informed consent
• Secondary malignancies other than basal cell carcinoma of the skin or carcinoma in situ within the last five years
• History of seizures or requirement for medicines, such as haldol, for controlling mental disorders
• Concurrent need for corticosteroid therapy
• Active connective tissue disease
• Pleural effusion, pericardial effusion or ascites
• Patients allergic to gentamicin
• Patients with positive PCR for hepatitis C or hepatitis B
• Patients with hypersensitivity to E. coli - derived preparations
• Patients with systemic infection at time of IL2 therapy
• Patients who previously have had more than 50% of their pelvic area irradiated
• Patients with pulmonary function tests that show diffusion capacity (corrected) < 60%, and/or forced expiratory volume in 1 second (FEV1) < 65% of predicted