Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01318317
Other study ID # 09174
Secondary ID NCI-2011-0034409
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 19, 2011
Est. completion date December 30, 2024

Study information

Verified date February 2024
Source City of Hope Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 8
Est. completion date December 30, 2024
Est. primary completion date October 3, 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSCT
Biological:
Filgrastim
Given IV
Genetically Engineered Lymphocyte Therapy
Receive ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR
Other:
Laboratory Biomarker Analysis
Correlative studies
Procedure:
Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSCT
Drug:
Plerixafor
Given IV
Biological:
Rituximab
Given IV

Locations

Country Name City State
United States City of Hope Medical Center Duarte California

Sponsors (2)

Lead Sponsor Collaborator
City of Hope Medical Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Dose Limiting Toxicities (DLTs) Number of DLTs per dose level are reported.
A DLT is defined as:
Any grade 3 or higher toxicity, with the exception of expected adverse events; and designated as definitely or probably related (level of attribution) to the infusion of the TCM cells; and occurring within 28 days of T-cell infusion; Any toxicity requiring the use of steroids to ablate side effects attributable to the infusion of the TCM cells, and occurring within 28 days of T-cell infusion; Any toxicity which is a lower grade, but that increases in grade to a grade 3 or higher as a direct result of the TCM, and occurring within 28 days of T-cell infusion; Any grade 2 or greater autoimmune toxicity, and occurring within 28 days of T-cell infusion.
Within 28 days of T-cell infusion
Primary Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) Detection Above Background Peak expansion of WPRE is expressed in CAR copy number/mL of blood is summarized with median and range 28 days post T cell infusion
Primary Number of Days of Quantifiable CD19 CAR Post T-cell Infusion WPRE persistence of quantifiable CD19 CAR summarized with mean and standard deviation 28 days post T cell infusion
Secondary Failure to Engraft Count of participants who fail to engraft post transplant. Within 21 days post T-cell infusion
Secondary Progression-free Survival at 1 Year Estimated using the Kaplan-Meier methods.
Progression is defined using the revised IWG response criteria, as any new lesion or increase by =50% of previously involved sites from nadir.
Up to 1 year
See also
  Status Clinical Trial Phase
Withdrawn NCT04635683 - Lenalidomide, Umbralisib, and Ublituximab for the Treatment of Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma Phase 1
Completed NCT01527045 - Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies Phase 2
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
Active, not recruiting NCT01955499 - Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma Phase 1
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
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Terminated NCT00383565 - FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 2
Completed NCT00253630 - Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
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
Terminated NCT01678443 - Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies Phase 1
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
Active, not recruiting NCT04578600 - CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma Phase 1