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Monoclonal Antibody Therapy in Treating Patients With Recurrent Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

Primary Purpose

Leukemia, Lymphoma

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
B43-genistein immunoconjugate
Sponsored by
Parker Hughes Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent childhood acute lymphoblastic leukemia, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic 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 childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent small lymphocytic lymphoma

Eligibility Criteria

undefined - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Immunophenotypically proven B-cell acute lymphoblastic leukemia Relapsed at least once following standard induction chemotherapy M1, M2, M3 No CNS disease (including clinical signs of CNS disease) OR Immunophenotypically proven B-cell non-Hodgkin's lymphoma Refractory or resistant disease following up to 3 prior courses of combination chemotherapy Relapsed following bone marrow transplantation No CNS disease No AIDS-related or HTLV-1 associated lymphomas NHL must be one of the following types: Small lymphocytic lymphoma (consistent with chronic lymphoblastic leukemia) Follicular small cleaved cell lymphoma Follicular mixed cell lymphoma Follicular large cell lymphoma Diffuse small cleaved cell lymphoma Diffuse mixed cell lymphoma Diffuse large cell lymphoma Immunoblastic large cell lymphoma Diffuse small noncleaved cell lymphoma Must have greater than 20% CD19 antigen positive blasts in the bone marrow, peripheral blood, or biopsy (for NHL) at first diagnosis or relapse (non-T cell ALL with CD19 positivity pending allowed) Patients who have relapsed after bone marrow transplantation are eligible (no active acute or chronic graft versus host disease involving more than the skin) PATIENT CHARACTERISTICS: Age: 80 and under Performance status: Karnofsky 60-100% Zubrod 0-2 Life expectancy: At least 2 months Hematopoietic: Granulocytopenia, anemia, and/or thrombocytopenia allowed Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN OR Creatinine clearance or radioisotope GFR at least 70 mL/min Cardiovascular: Shortening fraction at least 27% by echocardiogram OR Cardiac ejection fraction greater than 50% by echocardiogram or gaited radionuclide Pulmonary: No dyspnea at rest No exercise intolerance No clinical evidence of significant restrictive pulmonary disease Pulse oximetry greater than 94% FEV1 or FVC greater than 60% DLCO at least 65 Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study HIV negative No uncontrolled diabetes mellitus No other serious uncontrolled medical condition No active uncontrolled infection requiring systemic antibiotics or antifungal medications Prior CNS toxicity no greater than grade 1 PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Recovered from prior biologic therapy Chemotherapy: See Disease Charactertistics At least 2 weeks since prior chemotherapy (4 weeks since nitrosoureas) and recovered Endocrine therapy: At least 1 week since prior high dose steroid therapy and recovered Radiotherapy: Not specified Surgery: Not specified

Sites / Locations

  • Children's Hospital Los Angeles
  • Children's National Medical Center
  • Parker Hughes Institute

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 7, 2000
Last Updated
September 19, 2013
Sponsor
Parker Hughes Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00004858
Brief Title
Monoclonal Antibody Therapy in Treating Patients With Recurrent Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
Official Title
A Phase I Study of B43-Genistein Immunoconjugate in Recurrent B-Lineage Acute Lymphoblastic Leukemia and Non Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2007
Overall Recruitment Status
Unknown status
Study Start Date
March 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Parker Hughes Cancer Center

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have recurrent acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose of B43-genistein immunoconjugate in patients with recurrent B-cell acute lymphoblastic leukemia or non-Hodgkin's lymphoma. II. Determine the systemic B43-genistein exposure levels in these patients. III. Determine the antileukemic activity of this regimen in these patients. IV. Monitor the development of human antimouse antibody in these patients on this regimen. OUTLINE: This is a dose escalation study. Patients receive B43-genistein immunoconjugate IV over 1 hour on days 1-3, 8-10, and 15-17. Treatment continues every 3 weeks in the absence of unacceptable toxicity or until disease progression. Cohorts of 3-6 patients receive escalating doses of B43-genistein immunoconjugate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 6 months. PROJECTED ACCRUAL: A minimum of 3-15 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
recurrent childhood acute lymphoblastic leukemia, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic 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 childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
B43-genistein immunoconjugate

10. Eligibility

Sex
All
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Immunophenotypically proven B-cell acute lymphoblastic leukemia Relapsed at least once following standard induction chemotherapy M1, M2, M3 No CNS disease (including clinical signs of CNS disease) OR Immunophenotypically proven B-cell non-Hodgkin's lymphoma Refractory or resistant disease following up to 3 prior courses of combination chemotherapy Relapsed following bone marrow transplantation No CNS disease No AIDS-related or HTLV-1 associated lymphomas NHL must be one of the following types: Small lymphocytic lymphoma (consistent with chronic lymphoblastic leukemia) Follicular small cleaved cell lymphoma Follicular mixed cell lymphoma Follicular large cell lymphoma Diffuse small cleaved cell lymphoma Diffuse mixed cell lymphoma Diffuse large cell lymphoma Immunoblastic large cell lymphoma Diffuse small noncleaved cell lymphoma Must have greater than 20% CD19 antigen positive blasts in the bone marrow, peripheral blood, or biopsy (for NHL) at first diagnosis or relapse (non-T cell ALL with CD19 positivity pending allowed) Patients who have relapsed after bone marrow transplantation are eligible (no active acute or chronic graft versus host disease involving more than the skin) PATIENT CHARACTERISTICS: Age: 80 and under Performance status: Karnofsky 60-100% Zubrod 0-2 Life expectancy: At least 2 months Hematopoietic: Granulocytopenia, anemia, and/or thrombocytopenia allowed Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN OR Creatinine clearance or radioisotope GFR at least 70 mL/min Cardiovascular: Shortening fraction at least 27% by echocardiogram OR Cardiac ejection fraction greater than 50% by echocardiogram or gaited radionuclide Pulmonary: No dyspnea at rest No exercise intolerance No clinical evidence of significant restrictive pulmonary disease Pulse oximetry greater than 94% FEV1 or FVC greater than 60% DLCO at least 65 Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study HIV negative No uncontrolled diabetes mellitus No other serious uncontrolled medical condition No active uncontrolled infection requiring systemic antibiotics or antifungal medications Prior CNS toxicity no greater than grade 1 PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Recovered from prior biologic therapy Chemotherapy: See Disease Charactertistics At least 2 weeks since prior chemotherapy (4 weeks since nitrosoureas) and recovered Endocrine therapy: At least 1 week since prior high dose steroid therapy and recovered Radiotherapy: Not specified Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fatih M. Uckun, MD
Organizational Affiliation
Parker Hughes Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
Parker Hughes Institute
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55113
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
10632319
Citation
Uckun FM, Messinger Y, Chen CL, O'Neill K, Myers DE, Goldman F, Hurvitz C, Casper JT, Levine A. Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor. Clin Cancer Res. 1999 Dec;5(12):3906-13.
Results Reference
result

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Monoclonal Antibody Therapy in Treating Patients With Recurrent Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

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