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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00621452
Other study ID # 2154.00
Secondary ID NCI-2010-00416
Status Completed
Phase Phase 1
First received February 21, 2008
Last updated August 4, 2014
Start date August 2007

Study information

Verified date August 2014
Source Fred Hutchinson Cancer Research Center
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date
Est. primary completion date January 2014
Accepts healthy volunteers No
Gender Both
Age group N/A and older
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Biological:
therapeutic autologous lymphocytes
Given IV
Drug:
cyclophosphamide
Given IV
Biological:
aldesleukin
Given subcutaneously
Genetic:
polymerase chain reaction
Correlative studies
gene rearrangement analysis
Correlative studies
Procedure:
lymph node biopsy
Optional correlative studies
Biological:
genetically engineered lymphocyte therapy
Receive genetically modified T cells
Procedure:
bone marrow aspiration
Optional correlative studies
Other:
flow cytometry
Correlative studies
laboratory biomarker analysis
Correlative studies
enzyme-linked immunosorbent assay
Correlative studies

Locations

Country Name City State
United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Feasibility of transfecting and expanding the necessary numbers of T cells and the types of problems and toxicities which might be encountered, graded according the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 A true grade 3 or higher toxicity rate in excess of 20% attributed to T cell infusions will be considered grounds for stopping the study and amending the protocol to lower the cell infusion doses. If there ever exists sufficient evidence to suggest that the true T cell-related toxicity rate (grade 3 or higher, with the exception of fever > 40 degrees Celsius lasting less than 24 hours) exceeds 20%, the study will be stopped. Up to 2 years after final T cell infusion Yes
Secondary Comparison of the percentages of CD20-specific T cells and malignant B cells present in the blood before and after each T cell infusion Numbers and percentages of CD20-specific T cells and of malignant B cells will also be quantified in lymph node (LN) and bone marrow (BM). Up to 4 weeks after the third infusion No
Secondary Immune response as assessed by ELISA and percent chromium release in cytotoxicity assays Means, medians and standard deviation (S.D.) of the Ab titers observed will be computed. Up to 12 months following treatment No
Secondary Absolute numbers of T cells expressing the chimeric T Cell receptor (cTCR) per cubic uL of blood Up to 1 year No
See also
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Active, not recruiting NCT02153580 - Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia Phase 1
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Terminated NCT02109224 - Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection Phase 1
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
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Completed NCT00006473 - Oxaliplatin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 2
Completed NCT00003196 - Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma N/A
Active, not recruiting NCT01318317 - Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma Phase 1/Phase 2
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Completed NCT01921387 - Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies Phase 1/Phase 2
Active, not recruiting NCT01815749 - Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma Phase 1
Recruiting NCT04007029 - Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia Phase 1
Completed NCT01267812 - Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation Phase 2
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1