Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Phase I Trial Of Intravenous Bispecific Antibody (4G7XH22) In Patients With Refractory Or Relapsed Non-Hodgkin's Lymphoma Or Chronic Lymphocytic Leukemia (CLL)

RATIONALE: Antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of antibody therapy in treating patients who have refractory or relapsed non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of bispecific antibody 4G7xH22 in patients with relapsed or refractory non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
• Assess the clinical toxicity of this antibody in these patients.

OUTLINE: This is a dose escalation study of bispecific antibody (BsAb) 4G7xH22.

Patients receive sargramostim (GM-CSF) subcutaneously on day 1 and BsAb 4G7xH22 IV over 2 hours on day 2. Treatment repeats weekly for a total of 3 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BsAb 4G7xH22 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 4 weeks, monthly for 3 months, and then periodically for 1 year.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of CD19+ non-Hodgkin's lymphoma or chronic lymphocytic leukemia

  • Primary refractory or multiply relapsed (after at least 2 prior chemotherapy regimens) disease
  • Ineligible for bone marrow or peripheral blood stem cell transplantation

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Absolute neutrophil count greater than 1,500/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• Alkaline phosphatase less than 2 times normal
• SGPT less than 2 times normal

Renal:

• Creatinine clearance greater than 50 mL/min

Other:

• No human-anti-murine-antibody response to prior murine monoclonal antibodies
• No immunological or inflammatory disease (e.g., lupus erythematosus)
• No active serious infection
• No other serious medical condition that would limit survival to less than 2 years
• No other active malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix
• No psychiatric or addictive disorder that would preclude study
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy allowed

Chemotherapy:

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent steroids for adrenal failure or adverse reactions to study drug allowed
• Concurrent hormonal therapy for non-disease related conditions (e.g., insulin for diabetes) allowed

Radiotherapy:

• Not specified

Surgery:

• Not specified