Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL
1 other identifier
interventional
30
1 country
2
Brief Summary
The team has developed the synthetic T cell receptor (TCR) and antigen receptor (STAR) T cells which were demonstrated safety in relapsed or refractory (r/r) B-cell non-Hodgkin' s lymphoma (B-NHL) (NCT05631912). Based on this research, allogeneic STAR-T cell products utilized the CRISPR-Cas9 gene editing tool to knock out endogenous receptor α constant (TRAC), human leukocyte antigen (HLA)-A/B, CIITA, and programmed death 1 (PD-1) genes simultaneously in T cells from healthy donors, and integrated the STAR molecule into the TRAC locus using adenovirus associated virus. This strategy can reduce graft-versus-host-disease (GvHD) toxicity and host-versus-graft response, decrease the sensitivity of STAR T cells to immunosuppressive signals, and improve their anti-tumor activity. In this single center, prospective, open-label, single-arm, phase 1/2 study, the safety and efficacy of allogeneic CD19-targeting STAR T cell therapy will be evaluated in patients with r/r B-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 Mar 2024
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2024
CompletedFirst Posted
Study publicly available on registry
March 20, 2024
CompletedStudy Start
First participant enrolled
March 20, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 20, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 20, 2027
ExpectedMarch 25, 2024
March 1, 2024
2 years
March 13, 2024
March 22, 2024
Conditions
Outcome Measures
Primary Outcomes (3)
Phase 1: Incidence of Adverse Events (AEs) defined as DLT
DLT is defined as any AE related to the investigational drug that occurs within 28 days after administration of the STAR T cells and meets any one of the criteria listed in the DLT criteria. Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) 2019 criteria. 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. * Grade 3 acute GVHD (aGVHD) that is not resolved to Grade 1 or 2 within 7 days, with the exception of isolated skin involvement aGVHD; * Grade 4 CRS or grade 3 CRS that is not resolved 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 AEs related to the STAR T that lasts for ≥14 days, except hematology toxicity.
12 months
Phase 1: RP2D
The RP2D was determined through phase 1 study.
12 months
Phase 2: Best objective Response Rate
The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the Lugano 2014 assessment criterion.
12 months
Secondary Outcomes (7)
Phase 2: Overall Survival (OS)
12 months after the first infusion of CD19-STAR T cells
Phase 2: Progression Free Survival (PFS)
12 months after the first infusion of CD19-STAR T cells
Phase 2: Time to response (TTR)
12 months
Phase 2: Duration of Response (DOR)
12 months
Pharmacokinetics: Number and copy number of CD19-STAR T cells (phase 1 and phase 2)
12 months
- +2 more secondary outcomes
Other Outcomes (1)
Phase 1: Levels of donor-specific anti-HLA antibodies (DSA) in blood.
12 months
Study Arms (1)
Allogeneic TRAC locus-inserted CD19-targeting STAR T cells
EXPERIMENTALA conditioning chemotherapy regimen of fludarabine and cyclophosphamide (FC regimen) will be administered followed by investigational treatment, allogeneic targeting CD19 synthetic T-cell receptor antigen receptor T cells.
Interventions
Phase 1 dose escalation (3+3): dose 1 (2×10\^6 cells/kg), dose 2 (6×10\^6 cells/kg), dose 3 (1.8×10\^7 cells/kg); Phase 2: dose of RP2D. No more than 5 × 10\^4 per kilogram of allogenic residual TCR-positive T cells harbouring in grafts can only be released for recipient infusion.
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:
- Evaluation of PD (never reached response or SD) after standard first-line treatment, 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:
- +19 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 CNS 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-PD-1 antibody, anti-programmed death ligand 1 (PD-L1) antibody, CD19/CD3-bispecific antibody, and so on.
- Confirmed evidence showing positiveness of anti-CD19 scFv reaction in patient serum.
- Prior CD19 targeted therapy.
- Prior CAR-T therapy or other genetically modified T cell therapy.
- Presence of DSA directed against STAR T cells.
- Patients who participated in other clinical trials within 4 weeks prior to enrollment.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853, China
School of medicine, Tsinghua University & Changping Laboratory
Beijing, China
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director of Biotherapeutic Department
Study Record Dates
First Submitted
March 13, 2024
First Posted
March 20, 2024
Study Start
March 20, 2024
Primary Completion
March 20, 2026
Study Completion (Estimated)
March 20, 2027
Last Updated
March 25, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will not share