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

NCT ID: NCT00182650

Last Updated: 2009-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-06-30

Study Completion Date

2008-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lymphoma

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

aldesleukin

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

therapeutic autologous lymphocytes

Intervention Type BIOLOGICAL

fludarabine phosphate

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion 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
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R21CA105824

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-IRB-01160

Identifier Type: -

Identifier Source: secondary_id

CDR0000438797

Identifier Type: -

Identifier Source: org_study_id