ssCART-19

Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

P1/2, N=27, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

No abstract available

P2, N=50, Not yet recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

P1/2, N=27, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

All patients received lymphodepletion with fludarabine (30 mg/m2 /d) and cyclophosphamide (300 mg/m2 /d) -based conditioning regimens on day −5 to −3...Among them, 8 patients with CML-LBC and 92 ph+ ALL patients received single CD19 CAR T therapy, others received tandem CD19/CD22 CAR T. The baseline characteristics of all patients were shown in Table 1... Worser sustained antitumor efficacy and long-term survival with CAR T-cells therapy in patients with CML-LBC compared to ph+ ALL patients, and ABL kinase region mutation is an independent risk factor for CR and LFS.

P1, N=10, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Feb 2024 --> Dec 2025 | Trial primary completion date: Aug 2023 --> Dec 2024

P1/2, N=40, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Dec 2024

In this phase 1/2 clinical trial conducted at two centers, we compared the efficacy and safety of ssCART-19 to classical CART-19 cells (cCART-19) in patients with r/r B-ALL (NCT03919240)...Lymphodepletion (fludarabine at 30 mg/m2/day and cyclophosphamide at 300 mg/m2/day) was conducted on days -5, -4, and -3 before infusion... Our clinical studies demonstrated the safety and high efficacy of ssCART-19 with IL-6 gene silencing in patients with relapsed/refractory B-ALL. These findings support the potential of ssCART-19 as a promising therapeutic approach for this challenging patient population.

Afterwards, autologous CAR T-cells targeting CD22 and CD19 (CAR-T 1, co-stimulatory molecule was 4-1BB and infusion dose was 5×106/kg, respectively) were sequential infused after lymphodepletion chemotherapy with fludarabine and cytophosphamide...Two patients with Ph- B-ALL relapsed at 5 and 6 months after auto-HSCT and were treated with blinatumomab... Our preliminary study demonstrated that CD22/CD19 CAR-T and Auto-HSCT "Sandwich" strategy as a consolidation strategy showed favorable safety and efficacy in Ph- B-ALL. CD22/CD19 CAR-T resulted in deeper remission before transplantation. The new strategy may benefit patients from LFS and OS.

A total of 5 patients with severe cytokine release syndrome (Grade ≥ 3) were observed, including 2 patients in the single CD19 CAR-T group, 2 patients in the tandem CD19/CD22 CAR-T group, and 1 patient in the sequential CD19 and CD22 CAR-T group. Of the 23 patients who achieved CR, 4 patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 3 patients received decitabine (DAC) consolidation.With the median follow-up of 25.5 months (range, 1.1 to 33.5), the 2-year overall survival, leukemia-free survival (LFS) and cumulative incidence of relapse rates were 23.7%, 30.5% and 69.5%, respectively. Multivariate Cox regression analyses showed that a better LFS related to the absence of high-risk cytogenetics and genetic characteristics, DAC combination with fludarabine and cyclophosphamide lymphodepletion regimen, and bridging allo-HSCT or DAC consolidation. Our study showed that the second infusion of tandem CD19/CD22 CAR-T therapy obtains a better response than other infusion strategies. Bridging allo-HSCT or DAC consolidation had a significant survival benefit in patients with CR after the second CAR-T therapy.

Patients received fractionated infusions split over 3 days (10%; 30%; 60%) after lymphodepleting chemotherapy (3 days fludarabine and cyclophosphamide). ssCART-19 CAR-T cell therapy can effectively reduce the incidence of severe CRS and ICANS, especially control the occurrence of ICANS. And ssCART-19 achieved a high rate of remission in adult patients with R/R B-cell ALL. The ORR within 3 months were 83.3%.

Multivariable analysis in CR patients showed that a low frequency of relapse, a low tumor burden, minimal residual disease-negative CR and bridging to transplantation were independently associated with better leukemia-free survival. Our findings suggested that tandem CD19/CD22 CAR T-cell therapy obtains a better response than CD19 CAR T-cell therapy and a similar response to sequential CD19/CD22 CAR T-cell therapy.

P1/2, N=27, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

P1, N=18, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial primary completion date: May 2022 --> Dec 2023

P1/2, N=10, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Aug 2023 --> Aug 2024

The main purpose of this study is to observe the safety and efficacy of CD22/CD19 CAR-T bridging to autologous stem cell transplantation (auto-HSCT) in B-ALL patients...Afterwards, autologous CAR T-cells targeting CD22 and CD19 (co-stimulatory molecule was 4-1BB and infusion dose was 5×106/kg, respectively) were sequential infused after lymphodepletion chemotherapy with fludarabine and cytophosphamide... Our preliminary study demonstrated that autologous CD22 and CD19 CAR-T cell infusion bridging auto-HSCT as a consolidation strategy showed favorable safety and efficacy in B-ALL. The harvest of autologous stem cells after CAR-T cell therapy allows the persistence of CAR-T cells in the stem cells, which may explain the persistence of CAR-T cells after autologous transplantation despite the myeloablative conditioning regimen used in our study.

We conducted a phase II clinical trial of ssCAR-T-19 cells, anti-CD19 CAR-T cells with shRNA targeting IL-6, in 61 patients with r/r B-ALL...A multivariable analysis of baseline characteristics identified high bone marrow disease burden and poor genetic risk before infusion as independent risk factors for sCRS. After infusion, patients with sCRS exhibited larger expansion of ssCAR-T-19 cells, higher peak levels of IL-6, IL-10, and IFN-γ, and suffered more severe hematological and non-hematological toxicities compared with those with mCRS.

P1, N=10, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Feb 2020 --> Feb 2024 | Trial primary completion date: Aug 2019 --> Aug 2023

P1/2, N=40, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Sep 2020 --> Sep 2024 | Trial primary completion date: Sep 2019 --> Sep 2023

P1/2, N=27, Recruiting, The First Affiliated Hospital of Soochow University | Phase classification: P2 --> P1/2 | N=13 --> 27 | Active, not recruiting --> Recruiting

P2, N=13, Active, not recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

ssCART-19 DNA was found in the brains of treated animals, however no significant central nervous system toxicity was observed. These data were used to support an investigational new drug (IND) application of ssCART-19 for clinical trial in China.

Tandem CD19/CD22 dual targets CAR-T cells therapy obtains superior CR rate than single CD19 and sequential CD19/CD22 CAR-T cells therapy. This provides an effective treatment option for R/R B-ALL patients with chemotherapy resistance.

P1, N=18, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd