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

NCT00621452 | Completed Phase 1 DMC

• 2 other identifiers: 2154.00NCI-2010-00416
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; B-cell Chronic Lymphocytic Leukemia; 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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Comparison of the percentages of CD20-specific T cells and malignant B cells present in the blood before and after each T cell infusion

  Up to 4 weeks after the third infusion

• Immune response as assessed by ELISA and percent chromium release in cytotoxicity assays

  Up to 12 months following treatment

• Absolute numbers of T cells expressing the chimeric T Cell receptor (cTCR) per cubic uL of blood

  Up to 1 year

Study Arms (1)

Treatment (autologous CD20 specific T-cells)

EXPERIMENTAL

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.

Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide; Biological: aldesleukin; Genetic: polymerase chain reaction; Genetic: gene rearrangement analysis; Procedure: lymph node biopsy; Biological: genetically engineered lymphocyte therapy; Procedure: bone marrow aspiration; Other: flow cytometry; Other: laboratory biomarker analysis; Other: enzyme-linked immunosorbent assay

Interventions

therapeutic autologous lymphocytes BIOLOGICAL

Given IV

Also known as: AL, Autologous Lymphocytes, autologous T cells

Treatment (autologous CD20 specific T-cells)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (autologous CD20 specific T-cells)

aldesleukin BIOLOGICAL

Given subcutaneously

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (autologous CD20 specific T-cells)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment (autologous CD20 specific T-cells)

gene rearrangement analysis GENETIC

Correlative studies

Treatment (autologous CD20 specific T-cells)

lymph node biopsy PROCEDURE

Optional correlative studies

Also known as: Biopsy of Lymph Node

Treatment (autologous CD20 specific T-cells)

genetically engineered lymphocyte therapy BIOLOGICAL

Receive genetically modified T cells

Treatment (autologous CD20 specific T-cells)

bone marrow aspiration PROCEDURE

Optional correlative studies

Treatment (autologous CD20 specific T-cells)

flow cytometry OTHER

Correlative studies

Treatment (autologous CD20 specific T-cells)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (autologous CD20 specific T-cells)

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Treatment (autologous CD20 specific T-cells)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 22308288 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia

Interventions

Cyclophosphamide; aldesleukin; Interleukin-2; Polymerase Chain Reaction; Gene Rearrangement; Sentinel Lymph Node Biopsy; Flow Cytometry; Enzyme-Linked Immunosorbent Assay

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Genetic Phenomena; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Lymph Node Excision; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Immunoenzyme Techniques; Immunoassay; Immunologic Techniques; Immunosorbent Techniques; Immunohistochemistry; Molecular Probe Techniques

Study Officials

• Brian Till

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2008
• First Posted: February 22, 2008
• Study Start: August 1, 2007
• Primary Completion: January 1, 2014
• Last Updated: August 6, 2014

Record last verified: 2014-08

Locations

US (1)