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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: bispecific antibody 4G7xH22
* Biological: sargramostim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Antibody | Biological: bispecific antibody 4G7xH22<br> <br> Biological: sargramostim<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Toxicity | This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb). | day 1-29 | 
| Determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of BsAb 4G7 x 22 | This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb). | Day 1-29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Markers of Macrophage Activation | This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb). | Day 1 Hours 0,2,4,6,24, day 15 Hours 0,2,4,6,24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory chronic lymphocytic leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma