Antibody Therapy in Treating Patients With 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