Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma

OBJECTIVES:

• Determine the toxicity of high-dose combination chemotherapy comprising cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with non-Hodgkin's lymphoma.
• Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this regimen.
• Determine whether ATC traffic to tumor sites in select patients treated with this regimen.
• Assess the immune reconstitution of B cells and incidence of infection in patients treated with this regimen.
• Compare relapse rates and overall survival of patients treated with this regimen with historical controls.

OUTLINE: This is a dose-escalation study of activated T cells.

• Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes are treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC).
• High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day -7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3, and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.
• Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total of four infusions.

Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed CD20+ non-Hodgkin's lymphoma

• Disease is refractory, relapsed, or in remission
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin > 8 g/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 50,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• SGOT or SGPT ≤ 2.5 times normal
• No history of severe hepatic dysfunction

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• No uncompensated major adrenal dysfunction
• BUN < 1.5 times normal

Cardiovascular

• No severe cardiac dysfunction
• No major heart disease
• LVEF ≥ 50% by MUGA
• No uncontrolled hypertension
• No congenital or acquired heart disease or cardiac arrhythmias unless cardiac consult and evaluation are done

Pulmonary

• DLCO ≥ 50% of normal
• No symptomatic obstructive or restrictive disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infections
• HIV negative
• No significant skin breakdown from tumor or other diseases
• Dental evaluation and teeth cleaning with no potential sources of infection required
• No uncompensated major thyroid dysfunction

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior stem cell transplantation

Chemotherapy

• No prior total doxorubicin or daunorubicin dose ≥ 450 mg/m^2 unless endomyocardial biopsy shows < grade 2 drug effect AND ejection fraction ≥ 50% by gated blood pool scan

Endocrine therapy

• No concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for diabetes)