Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT04545762|
Recruitment Status : Recruiting
First Posted : September 11, 2020
Last Update Posted : September 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|Refractory Non-Hodgkin Lymphoma Burkitt Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Lymphoplasmacytic Lymphoma Primary Mediastinal Large B Cell Lymphoma Diffuse Large B Cell Lymphoma Small Lymphocytic Lymphoma Transformed Lymphoma||Drug: Fludarabine Drug: Cyclophosphamide Biological: anti-CD19 CAR-T cells||Phase 1|
This is an open-label, pilot, phase 1 study to determine the safety profile of anti-CD19 CAR-T cell infusion in participants with R/R B-cell NHL. The dose-finding cohorts in this study will evaluate and define the safe dose of anti-CD19 CAR-T cells. Using a "3+3" design, participants will be enrolled sequentially to each dose level. A dose expansion will then occur at the maximum tolerated dose (MTD) and dose levels that have not exceeded the MTD.
Up to 36 participants will be enrolled and treated. Each subject will provide consent and be evaluated for study eligibility. Eligible subjects will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. The CAR T cells will be produced using the Miltenyi Prodigy and an FDA compliant Lentigen CD19 targeted lentiviral vector. After successful generation of the anti-CD19 CAR-T cells (drug product (DP)), subjects will undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest. A single infusion of anti-CD19 CAR-T cells at the starting dose of 5 x 105 cells/kg will be given on Day=0. Following treatment with DP, subjects will be followed on this study for 12 months for safety, disease status, and survival. For long term follow-up, participants will be followed for 15 years.
- To evaluate the safety of administering chimeric antigen receptor T cells targeting CD-19 to patients with relapsed or refractory CD19+ B-cell nonHodgkin lymphoma (NHL).
- To determine the recommended phase 2 dose (RP2D) for this cellular therapy.
- To assess the safety and toxicity of cell collection and infusion of CAR-T cells targeting CD19 in patients with relapsed or refractory CD19+ B cell NHL.
- To describe the efficacy of chimeric antigen receptor T cells targeting CD-19 in patients with relapsed or refractory CD19+ B cell NHL.
- To evaluate the feasibility of CD19 CAR T cell manufacturing for patients with relapsed or refractory CD19+ B cell NHL of local manufacturing and ability to produce adequate quantities of vector positive T-cells
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma|
|Actual Study Start Date :||September 11, 2020|
|Estimated Primary Completion Date :||October 31, 2023|
|Estimated Study Completion Date :||October 31, 2023|
Experimental: Treatment Regimen
Apheresis (1 day): Autologous lymphocytes/ mononuclear cell collection will be collected through standard apheresis procedures as per University of California, San Francisco (UCSF) institutional practices
CAR-T cell manufacturing (estimated ~13-14 days)
Lymphodepleting chemotherapy: 3 days of immunosuppressive chemotherapy. Cyclophosphamide given at a dose of 300 mg/m2/IV and fludarabine given at 30 mg/m2 /IV on days -5, -4, and -3.
CAR-T cell infusion (1 day): The infusion of CAR-T cells targeting CD19 will occur over 5-30 minutes.
Given intravenously (IV)
Given intravenously (IV)
Biological: anti-CD19 CAR-T cells
- Proportion of participants with treatment-emergent adverse events (AEs) [ Time Frame: From initiation of study treatment to 12 months following CAR-T infusion, approximately 15 months ]All subjects enrolled in this phase I study who actually received study drug (anti-CD19 CAR-T infusion) will be included in the analysis. Proportion of participants with treatment-emergent adverse events of CAR-T in B-cell NHL, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0), revised Cytokine Release Syndrome (CRS) grading criteria, and American Society for Transplantation and Cellular Therapy (ASTCT) immune effector cell (IEC) -associated neurotoxicity syndrome (ICANS) Consensus Grading for Adults (for neurotoxicity grading).
- Proportion of participants who experience a dose-limiting toxicity (DLT) [ Time Frame: From initiation of study treatment to 30 days following CAR-T infusion ]A DLT includes those AEs graded according to CTCAE version 5.0, with the exceptions of CRS and neurotoxicity, which are graded using CRS and ICANS criteria. DLTs must 1) be suspected to be secondary to CAR-T cell infusion, 2) occur during the first 30 days after infusion and 3) meet the following criteria: 1. Grade 3 or 4 non-hematologic toxicities of any duration, with the following exceptions: Grade 3 laboratory abnormalities without associated symptomatology or clinical consequence that resolve in < 7 days; AEs associated with Grade <= 2 CRS; Toxicities associated with Grade 3 CRS (except cardiac or pulmonary organ toxicity) that improves to grade <= 2 within 3 days of intervention; isolated renal or hepatic grade 3 organ toxicity that does not resolve within 7 days; Laboratory abnormalities compatible with tumor lysis syndrome; Grade 4 hematological toxicity that persists at grade >= 3 despite maximum supportive care for >21 days.
- Proportion of participants with delayed infusion due to study-related adverse events [ Time Frame: From T-cell collection to end of infusion, approximately 18 days ]The proportion of participants who have their infusion delayed due to and AE will be reported.
- Table of adverse events related to collection and infusion of CAR-T cells [ Time Frame: From T-cell collection to end of infusion, approximately 18 days ]Frequency and severity for each adverse event of collection and infusion of CAR-T cells targeting CD19 in participants with relapsed B cell Non-Hodgkins Lymphoma
- Response rates over time [ Time Frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months ]Response rates will be categorized by overall, partial, and complete and will be reported as proportions at different time points across the study
- Best response rates [ Time Frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months ]Best overall, best partial, and best complete response rates will be calculated for the study overall. These will be reported cumulatively across the study population and across disease subtypes in a table format. Any comparisons will be hypothesis-generating and will be performed using Fisher's exact or the Chi-square test.
- Duration of response [ Time Frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months ]This is measured, only in responders, from the documented beginning of response (CR or PR) to the time of relapse
- Progression-free survival (PFS) [ Time Frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months ]PFS is defined as the time from entry onto study until lymphoma progression or death from any cause at 12 months after receiving CAR-T infusion.
- Overall Survival [ Time Frame: Up to 15 years ]Defined as the time from entry onto study until death from any cause
- Proportion of subjects for whom CD19 CAR T-cell therapy is manufactured [ Time Frame: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days ]Feasibility will be assessed by the proportion of subjects for whom the ability to produce adequate quantities of vector.
- Proportion of participants who complete study treatment [ Time Frame: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days ]Feasibility will be assessed by the proportion of subjects who complete the study regimen
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04545762
|Contact: Julie McCluggage, RNfirstname.lastname@example.org|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Julie McCluggage 877-827-3222 email@example.com|
|Principal Investigator: C. Babis Andreadis, MD|
|Principal Investigator:||C. Babis Andreadis, MD||University of California, San Francisco|