Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01318317
First received: March 16, 2011
Last updated: August 1, 2014
Last verified: August 2014
  Purpose

This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL


Condition Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Procedure: peripheral blood stem cell transplantation (PBSCT)
Biological: filgrastim
Genetic: polymerase chain reaction
Biological: rituximab
Biological: genetically engineered lymphocyte therapy
Other: laboratory biomarker analysis
Drug: plerixafor
Procedure: autologous hematopoietic stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Cellular Immunotherapy Using Central Memory-Enriched CD8+ T Cells Lentivirally Transduced to Express A CD19-Specific Chimeric Immunoreceptor Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • MTD based on DLTs and defining the full toxicity profile (Phase I) [ Time Frame: Within 28 days of T-cell infusion ] [ Designated as safety issue: Yes ]
    Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity. Determination of the full toxicity profile will include analyses of adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  • Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) detection above background (Phase II) [ Time Frame: 28 days after T cell infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rates of engraftment and persistence [ Time Frame: 28 days after T cell infusion ] [ Designated as safety issue: No ]
    Rates and associated 95% confidence intervals will be estimated.

  • Failure to engraft [ Time Frame: Within 21 days after T-cell infusion ] [ Designated as safety issue: No ]
    Rates and associated 95% confidence intervals will be estimated.

  • Progression-free survival [ Time Frame: Up to at least 15 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier methods.

  • Overall survival [ Time Frame: Up to at least 15 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier methods.


Estimated Enrollment: 57
Study Start Date: September 2011
Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cellular adoptive immunotherapy following PBSCT)
Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
Procedure: peripheral blood stem cell transplantation (PBSCT)
Undergo autologous PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Biological: filgrastim
Given IV
Other Names:
  • G-CSF
  • Neupogen
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Biological: genetically engineered lymphocyte therapy
Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR)
Other: laboratory biomarker analysis
Correlative studies
Drug: plerixafor
Given IV
Other Names:
  • AMD 3100
  • Mozobil
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSCT

Detailed Description:

PRIMARY OBJECTIVES: I. To assess the safety of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (TCM)-enriched cluster of differentiation (CD)8+ T cells genetically-modified to express a CD19-specific chimeric antigen receptor (CAR) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplantation (aHSCT) for research participants with high-risk intermediate grade B-lineage non-Hodgkin lymphomas who have relapsed after primary therapy, or who did not achieve complete remission with primary therapy. (Phase I)

II. To determine the maximum tolerated dose (MTD) on dose limiting toxicities (DLTs) and to describe the full toxicity profile. (Phase I)

III. To determine the rate of research participants receiving TCM-enriched CD8+ T cells genetically-modified to express a CD19-specific CAR for which the transferred cells are detected in the circulation 28 days (+/- 3 days) by woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) quantitative (Q)-polymerase chain reaction (PCR). (Phase II)

SECONDARY OBJECTIVES: I. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell product as it relates to the number of cells infused. (Phase II)

II. To study the impact of this therapeutic intervention on the development of CD19+ B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred CD19-specific T cells. (Phase II)

III. To describe the progression-free and overall survival of treated research participants on this protocol. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of genetically engineered lymphocyte therapy followed by a phase II study. Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with filgrastim and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

After completion of study treatment, patients are followed up periodically for at least 15 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate grade B-cell NHL (e.g., diffuse B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma)
  • History of relapse after achieving first remission with primary therapy, or failure to achieve remission with primary therapy - Life expectancy > 16 weeks
  • Karnofsky performance scale (KPS) >= 70%
  • Negative serum pregnancy test for women of childbearing potential
  • Research participant has an indication to be considered for autologous stem cell transplantation

Exclusion Criteria:

  • Fails to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study; evidence of understanding includes passing the Protocol Comprehensive Screening given by the Research Subject Advocate (RSA); a legal guardian may substitute for the research participant
  • Any standard contraindications to myeloablative HSCT per standard of care practices at COH
  • Dependence on corticosteroids
  • Currently enrolled in another investigational therapy protocol
  • Human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment
  • History of allogeneic HSCT or prior autologous HSCT
  • Active autoimmune disease requiring systemic immunosuppressive therapy
  • Research participant(s) who are to receive radioimmunotherapy (Zevalin-based)
  • based conditioning regimens
  • Research participant(s) with known active hepatitis B or C infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318317

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Leslie Popplewell City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01318317     History of Changes
Other Study ID Numbers: 09174, NCI-2011-00344, P50 CA107399
Study First Received: March 16, 2011
Last Updated: August 1, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014