Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Any age NCI FHCRC-1503.00 NCI-G01-1921, NCT00012207

Objectives

Primary

1. 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

1. 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.
2. Assess the trafficking of CD8+ cytotoxic T-lymphocyte clones to lymph nodes in these patients treated with this regimen.
3. Determine immune response and tumor response in patients treated with this regimen.

Entry 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/mm³



• No pulmonary involvement



• No CNS involvement

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

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

Expected Enrollment

A total of 12 patients will be accrued for this study within 4 years.

Outcomes

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

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

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/mm³), 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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

Oliver Press, MD, PhD, Protocol chair		Ph: 206-667-1872 Email: press@u.washington.edu

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
Washington
	Seattle
	Fred Hutchinson Cancer Research Center
		Oliver Press, MD, PhD	Ph:  206-667-1872
			Email: press@u.washington.edu
	University of Washington School of Medicine
		Clinical Trials Office - University of Washington School of Medicine	Ph:  206-616-8289

Registry Information
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
Trial Start Date		2000-09-26
Trial Completion Date		2011-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00012207
Date Submitted to PDQ		2001-01-06
Information Last Verified		2008-04-06
NCI Grant/Contract Number		CA15704, CA92302, CA117131

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