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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00182650

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated 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 :

Jun 1, 2004

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Mar 1, 2008

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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