Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Non-Hodgkin's Lymphoma

OBJECTIVES:

• Compare the response rates and time to treatment failure in patients with relapsed or refractory non-Hodgkin's lymphoma treated with iodine I 131 monoclonal antibody anti-B1, followed by high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM), and autologous peripheral blood stem cell transplantation (APBSCT) vs historical control patients treated with high-dose BEAM or carmustine, etoposide, cytarabine, and cyclophosphamide and APBSCT.
• Determine the safety of this regimen in these patients.

OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells or granulocyte macrophage colony-forming units. On day -19, patients receive unlabeled monoclonal antibody anti-B1 (MOAB anti-B1) IV followed by a dosimetric dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. On day -12, patients receive unlabeled MOAB anti-B1 IV followed by a therapeutic dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. Patients then receive high-dose chemotherapy comprising carmustine IV on day -6, etoposide IV and cytarabine IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day 0.

Patients are followed at days 30 and 100, at 6 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 5 years.

Inclusion criteria

• Diagnosis of non-Hodgkin's lymphoma (NHL) of one of the following types:

• Diffuse large B-cell
• Composite (at least 50% of tumor showing diffuse histology)
• Diffuse mixed cell
• Immunoblastic
• Relapsed or refractory disease sensitive to initial or subsequent conventional therapy (at least a partial response)
• Eligible for high-dose carmustine, etoposide, cytarabine, and melphalan protocol and autologous bone marrow transplantation or peripheral blood stem cell transplantation
• Evidence of CD20 antigen expression in tumor tissue
• Bidimensionally measurable disease
• Adequate peripheral blood stem cells

• At least 15,000,000 CD34+ cells/kg or
• At least 25,000 granulocyte macrophage colony-forming units/kg
• Age: 19 to 70
• Performance status: Karnofsky 70-100%
• Life expectancy: at least 4 months post-transplantation
• Bilirubin less than 2.0 mg/dL
• Creatinine less than 2.0 mg/dL
• Cardiac ejection fraction at least 40% for any of the following criteria:

• Age 60 and over
• Significant cardiac history (myocardial infarction or congestive heart failure)
• Received greater than 350 mg/m^2 of prior doxorubicin
• DLCO at least 50% of predicted
• HIV negative
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• At least 4 weeks since prior biologic therapy and recovered
• Human antimouse antibody negative
• At least 4 weeks since prior cytotoxic chemotherapy and recovered
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior immunosuppressants and recovered

Exclusion criteria

• No progressive disease in a field that has been previously irradiated with more than 3,500 cGy within the past year
• No known brain or leptomeningeal metastases
• No active obstructive hydronephrosis
• No New York Heart Association class III or IV heart disease
• No evidence of severe organ dysfunction
• No other major medical illnesses
• No active infection requiring IV antibiotics
• No other malignancy within the past 5 years except adequately treated skin cancer or carcinoma in situ of the cervix
• Not pregnant/negative pregnancy test
• No prior peripheral blood stem cell transplantation following high-dose chemotherapy or chemoradiotherapy
• No other concurrent biologic therapy for NHL
• No concurrent steroids except maintenance-dose steroids for noncancerous disease
• No concurrent external beam radiotherapy for NHL
• No other concurrent participation on protocol involving non-FDA-approved drugs or biologics