TRAC Locus-inserted CD19-targeting STAR-T Cell Therapy in r/r B-NHL
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|ClinicalTrials.gov Identifier: NCT05631912|
Recruitment Status : Recruiting
First Posted : November 30, 2022
Last Update Posted : November 30, 2022
|Condition or disease||Intervention/treatment||Phase|
|Non-hodgkin Lymphoma,B Cell||Biological: Autologous CD19-STAR-T cell Drug: Fludarabine Drug: Cyclophosphamide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Autologous TRAC Locus-inserted CD19-targeting Synthetic T-cell Receptor Antigen Receptor T (STAR-T) Cells for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma|
|Estimated Study Start Date :||December 15, 2022|
|Estimated Primary Completion Date :||December 15, 2024|
|Estimated Study Completion Date :||December 15, 2025|
Experimental: Autologous TRAC locus-inserted CD19-targeting STAR-T cells
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide (FC regimen) will be administered followed by investigational treatment, autologous targeting CD19 synthetic T-cell receptor antigen receptor T cells.
Post leukapheresis, administration of short half-life chemo-agents, Bruton tyrosine kinase inhibitor (BTKi) and/or dexamethasone should be considered to bridge the following FC regimen in patients with bulky tumor burden, rapidly aggressive progression, and/or indications of imperious symptom control.
Biological: Autologous CD19-STAR-T cell
Phase 1 dose escalation (3+3) : dose 1 (1×10^6 cells/kg) ,dose 2 (3×10^6 cells/kg) ,dose 3 (1×10^7 cells/kg); Phase 2 : Appropriate dose
Other Name: Autologous CD19-targeting synthetic T-cell receptor antigen receptor T cells
Intravenous fludarabine 25-30 mg/m^2/day on days -5, -4, and -3.
Other Name: Fludarabine Phosphate for Injection
Intravenous cyclophosphamide 300-500 mg/m^2/day on days -5, -4, and -3.
Other Name: Cyclophosphamide for Injection
- Phase 1: Incidence of Adverse Events (AEs) [ Time Frame: 12 months ]AE is defined as any adverse medical event from the date of randomization to 12 months after CD19-STAR-T cells infusion. Among them, CRS and ICANS were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
- Phase 1: Incidence of Dose-Limiting Toxicities (DLTs) [ Time Frame: First infusion date of CD19-STAR-T cells up to 28 days ]DLT was defined as CD19-STAR-T cells-related events with onset within first 28 days following infusion: The development of Grade (G) 3 or higher grade CRS lasting > 2 weeks; Any CD19-STAR-T cells-related AE requiring intubation; All G4 non-hematologic toxicities.
- Phase 1: Maximum tolerated dose (MTD) [ Time Frame: 12 months ]MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
- Phase 1: Recommended phase 2 dose (RP2D) [ Time Frame: 12 months ]The recommended dose for phase 2 was determined through phase 1 study.
- Phase 2: Best objective Response Rate [ Time Frame: 12 months ]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.
- Phase 2: Overall Survival (OS) [ Time Frame: 12 months after the first infusion of CD19-STAR-T cells ]OS is defined as the time from CD19-STAR-T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
- Phase 2: Progression Free Survival (PFS) [ Time Frame: 12 months after the first infusion of CD19-STAR-T cells ]PFS is defined as the time from the CD19-STAR-T cells infusion date to the date of disease progression assessed by investigators and based on the Lugano 2014 assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
- Phase 2: Time to response (TTR) [ Time Frame: 12 months ]TTR is defined as the time from CD19-STAR-T infusion to first assessed CR or PR by investigators and based on the Lugano 2014 assessment criterion.
- Phase 2: Duration of Response (DOR) [ Time Frame: 12 months ]DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the Lugano 2014 assessment criterion for r/r B-cell NHL, or death regardless of cause.
- Pharmacokinetics: Number and copy number of CD19-STAR-T cells (phase 1 and phase 2) [ Time Frame: 12 months ]Number and copy number of CD19-STAR-T cells were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (until CD19-STAR-T cells were not detected for two consecutive times) to detect the number and copy number of CD19-STAR-T cells, and to evaluate the pharmacokinetics of CD19-STAR-T.
- Pharmacokinetics: Persistence of CD19-STAR-T (phase 1 and phase 2) [ Time Frame: 12 months ]Persistence of CD19-STAR-T cell assessed by number in peripheral blood.
- Pharmacodynamics: Peak level of cytokines in serum (phase 1 and phase 2) [ Time Frame: Up to 28 days after infusion ]The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C reactive protein (CRP), ferritin. Peak was defined as the maximum post-baseline level of the cytokine.
- Relationship between infusion dose of CD19-STAR-T cells and efficacy [ Time Frame: 12 months ]Peripheral blood was collected at the day of infusion (day 1), day 4, day 7, day 11, day 14, day 28, at least once every month after 28 days, at least once every three months after half a year, and at least once every six months after a year. The researchers will analyze the relationship between the number of CD19-STAR-T cells, copy number, cytokines level, and efficacy of CD19-STAR-T cells. The number of STAR-T cells was detected by flow cytometry, and the copy number was detected by quantitative PCR (qPCR).
- To analyze the dynamic changes of STAR-T cells after infusion [ Time Frame: 12 months ]The dynamic changes of the number and copy number of STAR-T cells in patients after CD19-STAR-T treatment were analyzed. To summarize the characteristic of the peak, expansion pattern, continuous expansion time and evolution of STAR-T cells in vivo.
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): NCT05631912
|Contact: Weidong Han, Ph.Dfirstname.lastname@example.org|
|Contact: Yang liu, M.Demail@example.com|
|Biotherapeutic Department, Chinese PLA General Hospital||Recruiting|
|Beijing, Beijing, China, 100853|
|Contact: Weidong Han, Ph.D +86-010-66937463 firstname.lastname@example.org|
|Contact: Yang Liu, M.D. +86-010-66937463 email@example.com|
|Sub-Investigator: Yang Liu, M.D.|
|Sub-Investigator: Qingming Yang, M.D.|
|Sub-Investigator: Chunmeng Wang, M.S|
|Sub-Investigator: Jinhong Shi, M.S|
|School of medicine, Tsinghua University & Changping Laboratory||Recruiting|
|Beijing, Beijing, China|
|Contact: Xin Lin, Ph.D +86-010-62796319 firstname.lastname@example.org|
|Sub-Investigator: Xin Lin, Ph.D|
|Principal Investigator:||Weidong Han, Ph.D||Biotherapeutic Department, Chinese PLA General Hospital|