Leukemia, Lymphoma
Conditions
Keywords
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
Brief summary
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
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.
Interventions
BIOLOGICALbispecific antibody 4G7xH22
BIOLOGICALsargramostim
Sponsors
National Cancer Institute (NCI)
Dartmouth-Hitchcock Medical Center
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Toxicity | day 1-29 | 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). |
| Determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of BsAb 4G7 x 22 | Day 1-29 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Markers of Macrophage Activation | Day 1 Hours 0,2,4,6,24, day 15 Hours 0,2,4,6,24 | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm This is a Phase 1a/1b trial. three patients will be treated at dose level 1.If no Grade 3 or 4 toxicities, the next dose level will be given to a new cohort of three. If 1 of 3 patients suffer Grade 3 or 4 toxicity, an additional 3 patients will be treated at same dose level.if 1/6 have a Grade 3 or 4 toxicity, proceed to next dose level with a cohort of 3 patients. If \> 1/6 experience garde 3 or 4 toxicity, the DLT has been reached and the MTD is the dose level prior. Six patients will be treated at the MTD. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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).
Time frame: day 1-29
Population: 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).
Primary
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).
Time frame: Day 1-29
Secondary
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).
Time frame: Day 1 Hours 0,2,4,6,24, day 15 Hours 0,2,4,6,24