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

NCT ID: NCT00012207

Last Updated: 2010-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-09-30
• Study Completion Date: 2010-07-31

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.

Conditions

Leukemia; Lymphoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Oliver W. Press, MD, PhD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Washington School of Medicine

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18509084 (View on PubMed)

Other Identifiers

FHCRC-1503.00

Identifier Type: -

Identifier Source: secondary_id

NCI-G01-1921

Identifier Type: -

Identifier Source: secondary_id

CDR0000068494

Identifier Type: REGISTRY

Identifier Source: secondary_id

1503.00

Identifier Type: -

Identifier Source: org_study_id