Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT00621452

Last Updated: 2014-08-06

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

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Brief Summary

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

This phase I trial is studying the side effects of giving genetically engineered lymphocytes together with cyclophosphamide and aldesleukin in treating patients with relapsed or refractory mantle cell lymphoma or indolent B-cell non-Hodgkin lymphoma. Placing a gene that has been created in the laboratory into white blood cells may make the body build an immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Aldesleukin may stimulate the white blood cells to kill lymphoma cells. Giving genetically engineered lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for mantle cell lymphoma and B-cell non-Hodgkin lymphoma

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT00012207

Leukemia Lymphoma
COMPLETED PHASE1

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

NCT00005803

Prolymphocytic Leukemia Recurrent Adult Hodgkin Lymphoma Recurrent Childhood Hodgkin Lymphoma +11 more
COMPLETED PHASE1/PHASE2

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

NCT03277729

Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma +20 more
ACTIVE_NOT_RECRUITING PHASE1/PHASE2

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

NCT01865617

CD19-Positive Neoplastic Cells Present Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Chronic Lymphocytic Leukemia +10 more
COMPLETED PHASE1/PHASE2

Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia

NCT02153580

B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma B-Cell Prolymphocytic Leukemia High Grade B-Cell Lymphoma, Not Otherwise Specified +10 more
ACTIVE_NOT_RECRUITING PHASE1

Detailed Description

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

PRIMARY OBJECTIVES:

I. To assess the feasibility, safety and toxicity of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a "second generation' cluster of differentiation (CD)20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor in patients with recurrent or refractory CD20+ mantle cell or indolent lymphoma.

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence of adoptively transferred CD20-specific T cells transfected with a CD20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor.

II. To assess the trafficking of CD20-specific T cells to lymphoma masses. III. To evaluate the development of host anti-CD20 scFvFc:CD28:CD137:zeda chimeric immunoreceptor and anti-neomycin-resistance gene (NeoR) immune responses in study subjects.

OUTLINE:

CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes.

IMMUNOTHERAPY: Beginning 2 days after completion of cyclophosphamide, patients receive autologous CD20-specific T-cells IV over 30 minutes. Treatment repeats every 2-5 days for 3 courses.

MAINTENANCE THERAPY: Beginning 2 hours after the last T-cell infusion, patients receive low-dose aldesleukin subcutaneously twice daily for 14 days.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Subjects who have achieved at least a partial remission lasting a minimum of 6 months may, on a case-by-case basis, receive additional stored T cells following relapse.

After completion of study treatment, patients are followed up weekly for one month, monthly for 1 year, and then annually for up to 2 years.

Conditions

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

B-cell Chronic Lymphocytic Leukemia Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Splenic Marginal Zone Lymphoma Waldenström Macroglobulinemia

Study Design

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

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (autologous CD20 specific T-cells)

CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes.

IMMUNOTHERAPY: Beginning 2 days after completion of cyclophosphamide, patients receive autologous CD20-specific T-cells IV over 30 minutes. Treatment repeats every 2-5 days for 3 courses.

MAINTENANCE THERAPY: Beginning 2 hours after the last T-cell infusion, patients receive low-dose aldesleukin subcutaneously twice daily for 14 days.

Subjects who have achieved at least a partial remission lasting a minimum of 6 months may, on a case-by-case basis, receive additional stored T cells following relapse.

Group Type EXPERIMENTAL

therapeutic autologous lymphocytes

Intervention Type BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

aldesleukin

Intervention Type BIOLOGICAL

Given subcutaneously

polymerase chain reaction

Intervention Type GENETIC

Correlative studies

gene rearrangement analysis

Intervention Type GENETIC

Correlative studies

lymph node biopsy

Intervention Type PROCEDURE

Optional correlative studies

genetically engineered lymphocyte therapy

Intervention Type BIOLOGICAL

Receive genetically modified T cells

bone marrow aspiration

Intervention Type PROCEDURE

Optional correlative studies

flow cytometry

Intervention Type OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

enzyme-linked immunosorbent assay

Intervention Type OTHER

Correlative studies

Interventions

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

therapeutic autologous lymphocytes

Given IV

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type DRUG

aldesleukin

Given subcutaneously

Intervention Type BIOLOGICAL

polymerase chain reaction

Correlative studies

Intervention Type GENETIC

gene rearrangement analysis

Correlative studies

Intervention Type GENETIC

lymph node biopsy

Optional correlative studies

Intervention Type PROCEDURE

genetically engineered lymphocyte therapy

Receive genetically modified T cells

Intervention Type BIOLOGICAL

bone marrow aspiration

Optional correlative studies

Intervention Type PROCEDURE

flow cytometry

Correlative studies

Intervention Type OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

enzyme-linked immunosorbent assay

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

AL Autologous Lymphocytes autologous T cells CPM CTX Cytoxan Endoxan Endoxana IL-2 Proleukin recombinant human interleukin-2 recombinant interleukin-2 PCR Biopsy of Lymph Node ELISA

Eligibility Criteria

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

Inclusion Criteria

* Male or female subjects with immuno histopathologically documented CD20+ mantle cell lymphoma, follicular non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma/chronic lymphocytic leukemia, marginal zone, or lymphoplasmacytic NHL of any age, gender, or ethnic group who have relapsed or are refractory to conventional chemotherapy and who are not eligible for Fred Hutchinson Cancer Research Center (FHCRC)/University of Washington Medical Center (UWMC) transplant protocols (or who refuse participation in transplant protocols)
* Willingness to sign an informed consent and undergo study tests
* Willingness to receive cytoreductive chemotherapy, if necessary to debulk tumors prior to T cell administration, and to receive cyclophosphamide for lymphodepletion
* Serologic evidence of prior exposure to Epstein-Barr virus (EBV)
* Meets safety criteria to undergo leukapheresis
* Hemoglobin \> 9.0 gm/dL
* White blood cell (WBC) \> 2500 per microliter
* Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x Upper Limit of Normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x Upper Limit of Normal
* Creatinine =\< 1.6 mg/dL
* Willingness to use acceptable (barrier or hormonal methods) birth control as appropriate during the course of the study

Exclusion Criteria

* Treatment with fludarabine or cladribine within the previous 2 years prior to apheresis
* Known central nervous system involvement with NHL
* Pulmonary involvement with NHL; a diagnosis of pulmonary lymphoma will be based in part on findings from chest computed tomography (CT) and, if clinically appropriate, lung biopsy
* Exposure to chemotherapeutic agents (standard or experimental) or other immunosuppressive therapies less than four weeks prior to apheresis; patients must have recovered from acute side effects of such therapy
* Positive serology for human immunodeficiency virus (HIV)
* Active Hepatitis B or Hepatitis C infection
* History of hypersensitivity reactions to murine proteins or seropositivity for human anti-mouse antibody (HAMA)
* Requirement for corticosteroid therapy during the study period unless used specifically for amelioration of toxicity induced by transferred cells
* Treatment with anti-CD20 antibodies (rituximab, tositumomab, ibritumomab) within 4 months prior to start of T cell infusions
* Patients with lymph nodes in excess of 5 cm in diameter at time of T cell infusion
* Patients with \> 5000 circulating CD20+ lymphocytes per mm\^3 at time of T cell infusion
* Previous allogeneic stem cell transplantation
* Life expectancy less than 90 days
* Pregnancy
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

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Brian Till

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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

United States

References

Explore related publications, articles, or registry entries linked to this study.

Till BG, Jensen MC, Wang J, Qian X, Gopal AK, Maloney DG, Lindgren CG, Lin Y, Pagel JM, Budde LE, Raubitschek A, Forman SJ, Greenberg PD, Riddell SR, Press OW. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood. 2012 Apr 26;119(17):3940-50. doi: 10.1182/blood-2011-10-387969. Epub 2012 Feb 3.

Reference Type DERIVED
PMID: 22308288 (View on PubMed)

Other Identifiers

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

NCI-2010-00416

Identifier Type: REGISTRY

Identifier Source: secondary_id

2154.00

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.