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.

Condition	Treatment or Intervention	Phase
Lymphocytic Lymphoma Non-Hodgkin's Lymphoma	Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: antibody conjugate therapy  Procedure: colony-stimulating factor therapy  Procedure: antibody therapy  Procedure: cytokine therapy  Drug: bispecific antibody 4G7xH22  Drug: sargramostim	Phase I

Further Study Details: 

OBJECTIVES: I. 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. II. Assess the clinical toxicity of this antibody in these patients.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--Patient Characteristics--

Age: Over 18

Performance status: ECOG 0-2

Life expectancy: More than 3 months

Hematopoietic:

• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3
• Absolute neutrophil count greater than 1,500/mm3

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

New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States

Study chairs or principal investigators

Pamela Ely,  Study Chair,  Norris Cotton Cancer Center   

Study ID Numbers:  CDR0000068556; DMS-9806; NCI-G01-1936
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  April 10, 2001
ClinicalTrials.gov Identifier:  NCT00014560
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08