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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2014-00133 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 13277 | Other Identifier | City of Hope Medical Center | |
| P50CA107399 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase I trial studies the highest possible dose of memory enriched T cells that can be given following standard stem cell transplant before unmanageable side effects are seen in patients with B-cell non-Hodgkin lymphoma that has returned after previous treatment. A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Memory enriched T cells will be made from a patient's own T cells that are genetically modified in a laboratory. This means that the T cells are changed by inserting additional pieces of deoxyribonucleic acid (genetic material) into the cell to make it recognize and kill lymphoma cells. Memory enriched T cells may kill the cells that are not killed by stem cell transplant and may lower the chances of the cancer recurring.
PRIMARY OBJECTIVES: I. To assess the safety and determine the maximum tolerated dose (MTD) of each cellular immunotherapy product, cluster of differentiation (CD)19R (EQ) 28 zeta/truncated human epidermal growth factor receptor (EGFRt) + central memory T cell (Tcm) (Arm 1) and CD19R(EQ)28zeta/EGFRt+ naive memory T cell (TN/MEM) (Arm 2), in conjunction with a standard myeloablative autologous hematopoietic stem cell transplant (HSCT) for patients with high-risk intermediate or high grade B-lineage non-Hodgkin lymphomas.
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.
II. To study the impact of this therapeutic intervention on the development of normal CD19+ B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred autologous CD19R(EQ)28zeta/EGFRt+ Tcm or TN/MEM.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms. ARM 1: Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells intravenously (IV) over 10 minutes on day 2 or 3 following HSCT. ARM 2: Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT. Patients who experience disease progression and have not experienced serious treatment-related toxicities at greater than or equal to 100 days post T cell infusion will be allowed to receive an optional second T cell infusion.
After completion of study treatment, patients are followed up within 18-24 hours, then 18-72 hours, weekly for 1 month, monthly for 1 year, at 18, 24, and 36 months, and then annually thereafter for a minimum of 15 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 (autologous TCM-enriched T cells) | Experimental | Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT. |
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| Arm 2 (autologous TN/MEM-enriched T cells) | Experimental | Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells | Biological | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs), defined as any grade 3 or higher toxicity, any grade 3 or greater autoimmune toxicity, or failure for a research participant with documented T cell persistence to engraft by day 21 post HSCT | Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) and the Cytokine Release Syndrome (CRS) Clinical Symptoms & Revised Grading System. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated. | Up to 28 days |
| Incidence of adverse events attributable to the cellular immunotherapy product | Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated. | Up to 15 years |
| MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells based on DLTs | Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated. | 28 days |
| MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells based on DLTs | Toxicity and adverse events will be assessed using CTCAE v 4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Engraftment of the transferred T cell product | Rates and associated 95% confidence limits will be estimated. | Up to 28 days |
| Levels of CD19+ B-cell precursors in the bone marrow, used as a surrogate for the in vivo effector function of transferred CD19-specific T-cells |
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Inclusion Criteria:
ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS:
Exclusion Criteria:
Research participants with any uncontrolled illness including ongoing or active infections; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
Research participants with a history of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab
Research participants with known brain metastases (central nervous system [CNS] involvement either parenchymal or leptomeningeal involvement)
Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
History of allogeneic HSCT or prior autologous HSCT
Any standard contraindications to myeloablative HSCT per standard of care practices at COH
Dependence on corticosteroids
Currently receiving another investigational agent
Active autoimmune disease requiring systemic immunosuppressive therapy
Research participants will be excluded, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Budde, MD, PhD | City of Hope Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Medical Center | Duarte | California | 91010 | United States |
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| Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes | Biological | Given IV |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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CD19+ B cell levels will be reported over the study period using both descriptive statistics and graphical methods for each arm. |
| Up to 36 months |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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