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

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

This study is currently recruiting participants.
Information provided by National Cancer Institute (NCI)

This Tabular View shows the required WHO registration data elements as marked by ^†

Descriptive Information Fields

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

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.

Study Phase

Phase I

Study Type ^†

Interventional

Study Design ^†

Treatment, Open Label

Primary Outcome Measure ^†

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 [ Designated as safety issue: Yes ]

Secondary Outcome Measure ^†

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 [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
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 [ Designated as safety issue: Yes ]

Condition ^†

Leukemia
Lymphoma

Intervention ^†

Drug: aldesleukin
Drug: cyclophosphamide
Drug: prednisone
Drug: therapeutic autologous lymphocytes
Drug: vincristine
Procedure: adjuvant therapy

MEDLINE PMIDs

Links

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Recruitment Information Fields

Recruitment Status ^†

Recruiting

Enrollment ^†

Start Date ^†

September 2000

Completion Date

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

Gender

Both

Ages

Accepts Healthy Volunteers

Contacts ^††

Location Countries ^†

United States

Administrative Information Fields

NCT ID ^†

NCT00012207

Organization ID

CDR0000068494

Secondary IDs ^††

FHCRC-1503.00, NCI-G01-1921

Study Sponsor ^†

Fred Hutchinson Cancer Research Center

Collaborators ^††

National Cancer Institute (NCI)

Investigators ^†

Study Chair:

Oliver W. Press, MD, PhD

Fred Hutchinson Cancer Research Center

Information Provided By

National Cancer Institute (NCI)

Verification Date

April 2008

First Received Date ^†

March 3, 2001

Last Updated Date

May 23, 2008

^† Required WHO trial registration data element.
^†† WHO trial registration data element that is required only if it exists.