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

Primary Purpose

Leukemia, Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bispecific antibody 4G7xH22
sargramostim
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Norris Cotton Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Antibody

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

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).

Full Information

First Posted
April 10, 2001
Last Updated
April 2, 2018
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00014560
Brief Title
Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official Title
Phase I Trial Of Intravenous Bispecific Antibody (4G7XH22) In Patients With Refractory Or Relapsed Non-Hodgkin's Lymphoma Or Chronic Lymphocytic Leukemia (CLL)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Terminated
Why Stopped
Medarex (supplier of BsAb) stopped study due to toxicities experienced at other sites on unrelated trials halting manufacturing of BsAb
Study Start Date
September 28, 2000 (Actual)
Primary Completion Date
February 14, 2003 (Actual)
Study Completion Date
February 14, 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
Antibody
Intervention Type
Biological
Intervention Name(s)
bispecific antibody 4G7xH22
Intervention Type
Biological
Intervention Name(s)
sargramostim
Primary Outcome Measure Information:
Title
Clinical Toxicity
Description
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
Title
Determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of BsAb 4G7 x 22
Description
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 Outcome Measure Information:
Title
Serum Markers of Macrophage Activation
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pamela Ely, MD
Organizational Affiliation
Norris Cotton Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Norris Cotton Cancer Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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