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

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ClinicalTrials.gov Identifier: NCT00012207

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : August 24, 2010

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by:

Fred Hutchinson Cancer Research Center

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.

Condition or disease	Intervention/treatment	Phase
Leukemia Lymphoma	Biological: aldesleukin Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide Drug: prednisone Drug: vincristine sulfate Procedure: adjuvant therapy	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	12 participants
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	September 2000
Actual Study Completion Date :	July 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Follicular Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Marginal Zone Lymphoma

U.S. FDA Resources

Arms and Interventions

Outcome Measures

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

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00012207

Locations

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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
University of Washington School of Medicine
Seattle, Washington, United States, 98195

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

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Study Chair:	Oliver W. Press, MD, PhD	Fred Hutchinson Cancer Research Center

More Information

Publications of Results:

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.

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ClinicalTrials.gov Identifier:	NCT00012207 History of Changes
Other Study ID Numbers:	1503.00 FHCRC-1503.00 NCI-G01-1921 CDR0000068494 ( Registry Identifier: PDQ )
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	August 24, 2010
Last Verified:	August 2010

Keywords provided by Fred Hutchinson Cancer Research Center:


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

Additional relevant MeSH terms:

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Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Aldesleukin Prednisone Cyclophosphamide Vincristine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents	Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-HIV Agents

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