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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

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


PRIMARY OBJECTIVES: I. To assess the safety of cellular immunotherapy utilizing ex vivo
expanded autologous TCM-enriched CD8+ 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.


Inclusion Criteria:



- Verification of history of intermediate grade B-cell lineage lymphoma (e.g., diffuse
B-cell lymphoma, Mantle Cell lymphoma, transformed Follicular lymphoma), including
histological verification

- Imaging and/or histopathological confirmation of relapsed disease after achieving
first remission with primary therapy, or failure to achieve remission with primary
therapy

- Standard staging studies for extent of relapsed disease

- 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

MTD based on Dose Limiting Toxicity (DLT) (Phase I)

Outcome Description:

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.

Outcome Time Frame:

Within 30 days of T-cell infusion

Safety Issue:

Yes

Principal Investigator

Leslie Popplewell

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Federal Government

Study ID:

09174

NCT ID:

NCT01318317

Start Date:

September 2011

Completion Date:

Related Keywords:

  • 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
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Mantle-Cell

Name

Location

City of Hope Medical CenterDuarte, California  91010