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.
- 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
- 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
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
PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.
- Diagnosis of CD19+ non-Hodgkin's lymphoma or chronic lymphocytic leukemia
- Primary refractory or multiply relapsed (after at least 2 prior chemotherapy
- Ineligible for bone marrow or peripheral blood stem cell transplantation
- Over 18
- ECOG 0-2
- More than 3 months
- WBC greater than 3,000/mm^3
- Platelet count greater than 100,000/mm^3
- Absolute neutrophil count greater than 1,500/mm^3
- Bilirubin less than 1.5 mg/dL
- Alkaline phosphatase less than 2 times normal
- SGPT less than 2 times normal
- Creatinine clearance greater than 50 mL/min
- 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
- No psychiatric or addictive disorder that would preclude study
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Prior immunotherapy allowed
- See Disease Characteristics
- No concurrent chemotherapy
- Concurrent steroids for adrenal failure or adverse reactions to study drug allowed
- Concurrent hormonal therapy for non-disease related conditions (e.g., insulin for
- Not specified
- Not specified