Allogenic CD19-targeting CAR-γδT Cell Therapy in R/R NHL
A Phase 1/2 Clinical Trial of Gene-edited Allogenic CD19 Targeting Chimeric Antigen Receptor-γδT Cells Therapy in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
1 other identifier
interventional
30
1 country
2
Brief Summary
This is a single center, prospective, open-label, single-arm, phase 1/2 study for patients with r/r B-cell NHL to evaluate the safety and efficacy of gene edited allogenic CD19 CAR-γδT cells. The cells are from healthy adult volunteer donors that are gene edited ex vivo using CRISPR-Cas9 to weaken HLA expression and further to overcome host immune system rejection (HvGR). In this study, a second generation anti-CD19 CAR prototype was constructed, bearing murine FMC63 single-chain variant fragment (scFv) together with intracellular 4-1BB co-stimulatory and CD3ζ signaling domains linked by a CD8α sequence comprising the hinge and transmembrane domains. A total of around 30 patients with r/r B-cell NHL will be enrolled in the study and receive allogeneic CD19 CAR-γδT cell infusion. Phase 1 (n=9 to 12) is dose escalation part, and phase 2 (n=15 to 20) is expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of allogeneic CD19 CAR-γδT cell therapy in patients with r/r B-cell NHL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2022
Longer than P75 for phase_1
2 active sites
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
September 22, 2022
CompletedFirst Posted
Study publicly available on registry
September 26, 2022
CompletedStudy Start
First participant enrolled
December 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
August 6, 2025
August 1, 2025
4.1 years
September 22, 2022
August 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Phase 1: Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of lymphodepletion to 12 months after CD19 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
12 months
Phase 1: Incidence of Dose-Limiting Toxicities (DLTs)
DLT was defined as CD19 CAR-γδT cells-related events with onset within first 28 days following infusion: * Grade 3 aGVHD that does not resolve to Grade 1 or 2 within 7 days, with the exception of isolated skin involvement aGVHD; * Grade 4 CRS or grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks; * Grade 3 ICANS lasting for ≥7 days or Grade 4 ICANS; * Any other Grade ≥4 and Grade 3 AE related to the CAR-γδT that lasts for ≥14 days, except hematology toxicity.
First infusion date of CD19 CAR-γδT cells up to 28 days
Phase 1: Recommended Phase 2 Dose (RP2D)
The recommended dose for phase 2 was determined through phase 1 study.
12 months
Phase 2: Best Objective Response Rate
The incidence of complete response (CR) and partial response (PR) as the best response to treatment assessed by investigatorand based on the Lugano 2014 assessment criterion.
24 months
Phase 2: Best Complete Response Rate
The incidence of complete response (CR) as the best response to treatment assessed by investigatorand based on the Lugano 2014 assessment criterion.
24 months
Secondary Outcomes (7)
Phase 2: Overall Survival (OS)
24 months after the first infusion of CD19 CAR-γδT cells
Phase 2: Progression Free Survival (PFS)
24 months after the first infusion of CD19 CAR-γδT cells
Phase 2: Time to Response (TTR)
24 months
Phase 2: Duration of Response (DOR)
24 months
Pharmacokinetics: Number and Copy Number of CD19 CAR-γδT cells (phase 1 and phase 2)
12 months
- +2 more secondary outcomes
Other Outcomes (1)
Correlation Between Infusion Dose of CD19 CAR-γδT Cells and Efficacy
12 months
Study Arms (1)
Patients with refractory or relapsed B-cell NHL
EXPERIMENTALA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, allogenic targeting CD19 chimeric antigen receptor γδT cells.
Interventions
Phase 1 dose escalation (3+3) : dose 1 (6 × 10\^6 cells/kg) , dose 2 (1.2 × 10\^7 cells/kg), dose 3 (1.8 × 10\^7 cells/kg); Phase 2 : dose of RP2D.
Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.
Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.
Eligibility Criteria
You may qualify if:
- Age 18-75 (inclusive).
- Patients with histologically confirmed CD19-positive B-cell NHL, including the following types defined by the World Health Organization (WHO) 2016:
- Diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS), including Activated B-cell type (ABC）/Germinal center B-cell type（GCB）;
- Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
- Transformed follicular lymphoma (TFL);
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL);
- Follicular lymphoma (FL);
- Mantle cell lymphoma (MCL) (pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1);
- Marginal zone lymphoma (MZL), including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
- Relapse after treatment with ≥2 lines systemic therapy for all the above disease types, or refractory disease for aggressive types (DLBCL-NOS, PMBCL, TFL and HGBCL). Relapse disease is defined as disease progression after last regimen. Refractory disease is defined as no CR to first-line therapy:
- PD as best response to first-line therapy, or
- SD as best response after at least 4 cycles of first-line therapy (eg,4 cycles of R-CHOP), or
- PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months of therapy, or
- Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
- Individuals must have received adequate prior therapy:
- +15 more criteria
You may not qualify if:
- No obvious hereditary diseases.
- Able to understand the requirements and matters of the trial, and willing to participate in clinical research as required.
- Informed consent must be signed.
- During the screening period, there was central nervous system (CNS) invasion or a history of clinically significant central nervous system diseases, such as epilepsy and cerebrovascular diseases.
- Women who are pregnant or breastfeeding, or who do not agree to use effective contraception during treatment and during the subsequent 1 year.
- History of allogeneic hematopoietic stem cell transplantation, or organ transplantation.
- History of other malignancies that have not been in remission.
- Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.
- Received radiotherapy within 3 months before enrollment.
- Received immunotherapy drugs within 4 weeks before enrollment, such as anti-programmed death 1 (PD-1) antibody, anti-programmed death ligand 1 (PD-L1) antibody, CD19/CD3-bispecific antibody, and so on.
- Patients who received any immunocellular therapy within 3 months before enrollment.
- Confirmed evidence showing positiveness of anti-CD19 scFv reaction in patient serum.
- Patients who participated in other clinical trials within 4 weeks prior to enrollment.
- Uncontrolled infectious diseases or other serious illnesses, including but not limited to infections \[e.g., human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B (HBV) or C (HCV) infection\], congestive heart failure, unstable angina, arrhythmias, or that pose an unpredictable risk in the opinion of the attending physician.
- The presence of uncontrollable serous membrane fluid, such as massive pleural effusion or ascites.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
School of phamaceutical, Tsinghua University
Beijing, Beijing Municipality, China
Biotherapeutic Department, Chinese PLA General Hospital
Beijing, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Weidong Han, Ph.D
Biotherapeutic Department, Chinese PLA General Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director of Biotherapeutic Department
Study Record Dates
First Submitted
September 22, 2022
First Posted
September 26, 2022
Study Start
December 11, 2022
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2027
Last Updated
August 6, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share