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: March 7, 2014
Last verified: March 2014

March 16, 2011
March 7, 2014
September 2011
August 2022   (final data collection date for primary outcome measure)
  • 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 ]
  • Dose Limiting Toxicity (DLT) (Phase I) [ Time Frame: Within 30 days of T-cell infusion ] [ Designated as safety issue: Yes ]
    Defined as any grade 3 or higher toxicity and designated as definitely or probably related (level of attribution) to the infusion of the autologous ex vivo expanded central memory (TCM) cells; toxicity which is lower grade, but that increases in grade to a grade 3 or higher as a direct result of TCM infusion is also considered a DLT
  • Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) detection above background [ Time Frame: 30 days after T cell infusion ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01318317 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
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Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma
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

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

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 (HSCT) for research participant(s) 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 participant(s) receiving TCM-enriched CD8+ T cells genetically-modified to express a CD19-specific CAR for which the transferred cells are detected in the circulation for at least 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 participant(s) 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 G-CSF and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4 weeks of transplantation. 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 transplantation.

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

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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)
    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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
57
Not Provided
August 2022   (final data collection date for primary outcome measure)

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 active hepatitis B or C infection
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01318317
09174, NCI-2011-00344, P50 CA107399
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Leslie Popplewell City of Hope Medical Center
City of Hope Medical Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP