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Cellular Adoptive Immunotherapy in Treating Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00182650
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : December 29, 2009
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
City of Hope Medical Center

Study Description
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Brief Summary:

RATIONALE: Cellular adoptive immunotherapy uses a person's white blood cells that are treated in the laboratory to stimulate the immune system in different ways and stop cancer cells from growing. Rituximab and fludarabine may also prevent the body from making an immune response against the laboratory-treated white blood cells that are put back into the body. Interleukin-2 may help the laboratory-treated white blood cells stay in the body longer. Giving cellular adoptive immunotherapy together with rituximab, fludarabine, and interleukin-2 may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with relapsed or refractory follicular non-Hodgkin's lymphoma.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: aldesleukin Biological: rituximab Biological: therapeutic autologous lymphocytes Drug: fludarabine phosphate Phase 1

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and feasibility of cellular adoptive immunotherapy using autologous cytotoxic T lymphocytes genetically modified to express a CD19-specific chimeric immunoreceptor gene and HyTK selection/suicide gene in patients with relapsed or refractory follicular non-Hodgkin's lymphoma.

Secondary

  • Determine the in vivo persistence of adoptively transferred cytolytic T cells in patients treated with lymphodepleting therapy comprising rituximab and fludarabine.
  • Assess the development of host immune responses against the CD19-specific chimeric immunoreceptor gene and/or HyTK selection/suicide gene.
  • Determine the safety of low-dose interleukin-2 in supporting in vivo persistence of adoptively transferred cytotoxic T cells.
  • Determine the anti-tumor activity of this regimen in these patients.

OUTLINE: This is a nonrandomized, open-label, pilot study.

  • Leukapheresis: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). CD3-positive cytotoxic T lymphocytes (CTLs) are isolated and genetically modified to express a CD19-specific chimeric immunoreceptor and the HyTK fusion protein, and are then expanded in vitro.
  • Lymphodepleting therapy: Patients receive rituximab and fludarabine prior to T-cell infusions.
  • Cellular adoptive immunotherapy and interleukin-2 (IL-2): Patients receive a total of 5 infusions of genetically modified autologous T cells. Patients may receive low-dose IL-2 subcutaneously after infusions 3, 4, and 5.
  • Additional IL-2 therapy: After the completion of the last T-cell infusion, patients with evidence of adoptively transferred T cells may receive additional IL-2.

After completion of study treatment, patients are followed periodically for approximately 65 days and then annually for at least 15 years.

PROJECTED ACCRUAL: At least 5 patients will be accrued for this study within 3 years.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot/Feasibility Study To Evaluate The Safety Of Cellular Immunotherapy For CD19+ Follicular Lymphoma Using Autologous Cytolytic T Cells Genetically-Modified To Be CD19-Specific And Co-Express HyTK
Study Start Date : June 2004
Actual Primary Completion Date : March 2008
Actual Study Completion Date : March 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Outcome Measures
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Eligibility Criteria
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Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed follicular non-Hodgkin's lymphoma (NHL)

    • High-risk disease, as defined by any of the following:

      • Relapsed within 6 months after the last treatment
      • Failed to achieve a complete response during the last treatment
      • Relapsed after prior autologous hematopoietic stem cell transplantation (HSCT)
  • No current transformation of lymphoma (e.g., elements of intermediate- or high-grade lymphoma by biopsy)
  • No active CNS disease by lumbar puncture or radiology scan NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

  • 16 to 70

Performance status

  • Karnofsky 50-100%

Life expectancy

  • More than 16 weeks

Hematopoietic

  • Absolute neutrophil count > 500/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)* (unless due to Gilbert's disease)
  • ALT ≤ 2.5 times ULN* NOTE: *Unless due to NHL

Renal

  • Creatinine ≤ 1.5 times ULN* OR
  • Creatinine clearance ≥ 80 mL/min* NOTE: *Unless due to NHL

Immunologic

  • HIV negative
  • Epstein-Barr virus positive
  • No history of allergy or intolerance to ganciclovir

Other

  • Negative pregnancy test
  • No history of another malignancy except basal cell skin cancer or carcinoma in situ
  • No other uncontrolled or severe illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior allogeneic HSCT
  • No other immunotherapy during and for approximately 65 days after the last T-cell infusion, unless approved by the Principal Investigator (PI)

Chemotherapy

  • No other chemotherapy during and for approximately 65 days after the last T-cell infusion, unless approved by the PI

    • Patients may receive chemotherapy after leukapheresis while waiting for CD19-specific T cells to be manufactured

Endocrine therapy

  • No systemic corticosteroids during and for approximately 65 days after the last T-cell infusion, unless approved by the PI

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No concurrent participation in another investigational study
  • No immunosuppression agents or other investigational agents during and for approximately 65 days after the last T-cell infusion, unless approved by the PI
Contacts and Locations
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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): NCT00182650


Locations
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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
More Information
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ClinicalTrials.gov Identifier: NCT00182650    
Other Study ID Numbers: CDR0000438797
R21CA105824 ( U.S. NIH Grant/Contract )
P30CA033572 ( U.S. NIH Grant/Contract )
CHNMC-IRB-01160
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: December 29, 2009
Last Verified: December 2009
Keywords provided by City of Hope Medical Center:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Aldesleukin
Rituximab
Fludarabine
Fludarabine phosphate
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents