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Biological Therapy After Chemotherapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
aldesleukin
therapeutic autologous lymphocytes
cyclophosphamide
prednisone
vincristine sulfate
adjuvant therapy
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Immunohistopathologically documented relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma Indolent B-cell lymphomas including any of the following subtypes: Follicular lymphoma (grade I, II, or III) Small lymphocytic lymphoma or chronic lymphocytic leukemia Marginal zone lymphoma (splenic, nodal, and extra-nodal) Lymphoplasmacytoid lymphoma Ineligible for or unwilling to participate in other FHCRC/UWMC protocols Serological evidence of prior exposure to Epstein-Barr virus Must agree to undergo peripheral blood drawing, bone marrow biopsy, lymph node biopsy, and nuclear medicine imaging Must agree to cytoreductive chemotherapy if necessary to reduce lymph nodes to < 5 cm in diameter or circulating B lymphocyte counts to < 5,000/mm^3 No pulmonary involvement No CNS involvement PATIENT CHARACTERISTICS: Age: Any age Performance status: Not specified Life expectancy: At least 90 days Hematopoietic: Not specified Hepatic: No active hepatitis B infection Renal: Not specified Other: No HIV positivity Not pregnant or nursing Fertile patients must use effective contraception No history of hypersensitivity reactions to murine proteins PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 months since prior rituximab, tositumomab, or ibritumomab No prior allogeneic stem cell transplantation No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular products) Chemotherapy: At least 2 years since prior fludarabine or cladribine At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: No concurrent systemic corticosteroids except to treat toxicity from chemotherapy or cellular immunotherapy Radiotherapy: Not specified Surgery: Not specified Other: At least 4 weeks since prior immunosuppressive therapy and recovered No concurrent pentoxifylline No other concurrent investigational agents

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • Fred Hutchinson Cancer Research Center
  • University of Washington School of Medicine

Outcomes

Primary Outcome Measures

Safety and toxicity by NCI CTC toxicity scale in patients w/ recurr. or refract. CD20+ follicular lymphoma who are not candidates for high dose chemoradiotx and stem cell transplant during each infusion, weekly for 4 wks and then monthly for a yr

Secondary Outcome Measures

Duration of in vivo persistence of adoptively transferred CD20-specific CD8+ T cell clones by flow cytometry and quantitative polymerase chain reaction (qPCR) during each infusion, weekly for 4 weeks, and then monthly for a year
Trafficking of CD8+ CD20-specific T cell clones to lymph nodes by Gamma camera imaging during each infusion, weekly for 4 weeks, and then monthly for a year
Development of host anti-scFvFc:zeta (and anti-NeoR) immune responses by ELISA and chromium release assays during each infusion, weekly for 4 weeks, and then monthly for a year
Tumor responses to cyclophosphamide, vincristine, and prednisone (CVP) and to cytotoxic T-lymphocyte (CTL) infusions by Cheson criteria during each infusion, weekly for 4 weeks, and then monthly for a year

Full Information

First Posted
March 3, 2001
Last Updated
August 20, 2010
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00012207
Brief Title
Biological Therapy After Chemotherapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Phase I Study To Evaluate The Safety Of Cellular Immunotherapy Using Genetically Modified Autologous Cd20-Specific Cd8+ T Cell Clones For Patients With Relapsed Cd20+ Indolent Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
September 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining biological therapy with chemotherapy may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of biological therapy after chemotherapy in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: Primary Determine the safety and toxicity of cellular immunotherapy with autologous CD8+ cytotoxic T-lymphocyte clones after chemotherapy comprising cyclophosphamide, vincristine, and prednisone in patients with relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma. Secondary Determine the duration of in vivo persistence of adoptively transferred CD20-specific CD8+ cytotoxic T-lymphocyte clones in the absence and presence of subcutaneous interleukin-2 in these patients. Assess the trafficking of CD8+ cytotoxic T-lymphocyte clones to lymph nodes in these patients treated with this regimen. Determine immune response and tumor response in patients treated with this regimen. OUTLINE: This is an open-label, pilot study. Leukapheresis: Patients undergo leukapheresis. Selected CD20-specific CD8+ cells are cultured to expand the cytotoxic T lymphocytes (CTL), which are then cloned. Chemotherapy: Patients receive oral cyclophosphamide and oral prednisone on days 1-5 and vincristine IV on day 1. Courses repeat every 3-4 weeks for a total of 6 courses. Immune cell infusion: Beginning 4 weeks after the last course of chemotherapy (and lymph nodes ≤ 5 cm diameter or ≤ 5,000 circulating CD20+ lymphocytes/mm^3), patients receive autologous CD8+ CTL clones IV over 30 minutes. Courses repeat every 2-5 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. The last 6 patients receive interleukin-2 subcutaneously every 12 hours for 14 days, beginning 2 hours after the last infusion of CD8+ CTL clones. After course 2 or 3 of immune cells, all patients undergo surgical lymph node biopsy to determine if immune cells are moving to the lymph nodes. Patients are followed monthly for 1 year and then annually for 2 years. PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
aldesleukin
Intervention Type
Biological
Intervention Name(s)
therapeutic autologous lymphocytes
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Primary Outcome Measure Information:
Title
Safety and toxicity by NCI CTC toxicity scale in patients w/ recurr. or refract. CD20+ follicular lymphoma who are not candidates for high dose chemoradiotx and stem cell transplant during each infusion, weekly for 4 wks and then monthly for a yr
Secondary Outcome Measure Information:
Title
Duration of in vivo persistence of adoptively transferred CD20-specific CD8+ T cell clones by flow cytometry and quantitative polymerase chain reaction (qPCR) during each infusion, weekly for 4 weeks, and then monthly for a year
Title
Trafficking of CD8+ CD20-specific T cell clones to lymph nodes by Gamma camera imaging during each infusion, weekly for 4 weeks, and then monthly for a year
Title
Development of host anti-scFvFc:zeta (and anti-NeoR) immune responses by ELISA and chromium release assays during each infusion, weekly for 4 weeks, and then monthly for a year
Title
Tumor responses to cyclophosphamide, vincristine, and prednisone (CVP) and to cytotoxic T-lymphocyte (CTL) infusions by Cheson criteria during each infusion, weekly for 4 weeks, and then monthly for a year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Immunohistopathologically documented relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma Indolent B-cell lymphomas including any of the following subtypes: Follicular lymphoma (grade I, II, or III) Small lymphocytic lymphoma or chronic lymphocytic leukemia Marginal zone lymphoma (splenic, nodal, and extra-nodal) Lymphoplasmacytoid lymphoma Ineligible for or unwilling to participate in other FHCRC/UWMC protocols Serological evidence of prior exposure to Epstein-Barr virus Must agree to undergo peripheral blood drawing, bone marrow biopsy, lymph node biopsy, and nuclear medicine imaging Must agree to cytoreductive chemotherapy if necessary to reduce lymph nodes to < 5 cm in diameter or circulating B lymphocyte counts to < 5,000/mm^3 No pulmonary involvement No CNS involvement PATIENT CHARACTERISTICS: Age: Any age Performance status: Not specified Life expectancy: At least 90 days Hematopoietic: Not specified Hepatic: No active hepatitis B infection Renal: Not specified Other: No HIV positivity Not pregnant or nursing Fertile patients must use effective contraception No history of hypersensitivity reactions to murine proteins PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 months since prior rituximab, tositumomab, or ibritumomab No prior allogeneic stem cell transplantation No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular products) Chemotherapy: At least 2 years since prior fludarabine or cladribine At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: No concurrent systemic corticosteroids except to treat toxicity from chemotherapy or cellular immunotherapy Radiotherapy: Not specified Surgery: Not specified Other: At least 4 weeks since prior immunosuppressive therapy and recovered No concurrent pentoxifylline No other concurrent investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oliver W. Press, MD, PhD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
University of Washington School of Medicine
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18509084
Citation
Till BG, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, Qian X, James SE, Raubitschek A, Forman SJ, Gopal AK, Pagel JM, Lindgren CG, Greenberg PD, Riddell SR, Press OW. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008 Sep 15;112(6):2261-71. doi: 10.1182/blood-2007-12-128843. Epub 2008 May 28.
Results Reference
result

Learn more about this trial

Biological Therapy After Chemotherapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

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