Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
2 other identifiers
interventional
36
1 country
1
Brief Summary
This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2020
CompletedFirst Posted
Study publicly available on registry
September 11, 2020
CompletedStudy Start
First participant enrolled
September 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2026
January 14, 2026
August 1, 2025
6.1 years
August 31, 2020
January 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Proportion of participants with treatment-emergent adverse events (AEs)
Participants treated with conforming product who received the target doses of 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).
From initiation of study treatment to 12 months following CAR-T infusion, approximately 15 months
Proportion of participants who experience a dose-limiting toxicity (DLT) (Dose escalation)
A DLT includes 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 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.
From initiation of study treatment to 30 days following CAR-T infusion
Secondary Outcomes (10)
Proportion of participants with CAR-T infusion related adverse events (Dose Escalation)
From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Proportion of participants with delayed infusion due to study-related adverse events
From T-cell collection to end of infusion, approximately 18 days
Overall Response Rate (ORR)
From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Complete Response Rate
From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Partial Response Rate
From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
- +5 more secondary outcomes
Study Arms (2)
CLOSED TO ENROLLMENT: Dose escalation (CART-T Therapy)
EXPERIMENTALParticipants will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated \~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of CAR-T cells at an initial dose of 5 x 10\^5 cells/kg, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years.
Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy)
EXPERIMENTALParticipants with Burkitt lymphoma, or Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM) will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated \~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of the maximum tolerated dose of CAR-T cells established in the dose escalation phase, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years.
Interventions
Given intravenously (IV)
Given intravenously (IV)
Single infusion
Eligibility Criteria
You may qualify if:
- Dose expansion Cohorts:
- Cohort B (Burkitt):
- Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma
- Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.
- No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.
- Participants must have measurable disease as defined below:
- Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"
- Cohort M/W (Marginal/Waldenström):
- Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):
- o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.
- Participants must have measurable disease as defined below:
- o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia: must either have PET-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification" or serum monoclonal immunoglobulin M (IgM) paraprotein \> 0.5 g/dL.
- Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease necessitating systemic treatment.
- In addition, all participants must meet the following criteria:
- CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.
- +15 more criteria
You may not qualify if:
- Autologous transplant within 6 weeks of planned CAR-T cell infusion.
- Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.
- Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).
- Human immunodeficiency virus (HIV) seropositivity.
- Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded.)
- Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test.
- Participants with history of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
- History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
- Body weight \<40 kilograms(kg).
- Eligibility for Infusion of Investigational Product:
- No significant laboratory abnormalities. Laboratory result abnormalities that are considered not clinically significant by the principal investigator AND are not the result of a demonstrated active infection or an active central nervous system condition.
- ECOG performance status \< 2
- No evidence of uncontrolled intercurrent illness including, but not limited to ongoing or active infection, inflammatory response, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations.
- No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- C. Babis Andreadislead
- University of California, Daviscollaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
Related Publications (1)
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carrie Ho, MD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Clinical Medicine
Study Record Dates
First Submitted
August 31, 2020
First Posted
September 11, 2020
Study Start
September 11, 2020
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
October 31, 2026
Last Updated
January 14, 2026
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share