Early Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of SYNCAR-100 in the Treatment of CD19-Positive Relapsed or Refractory Acute B-Lymphoblastic Leukemia (R/R B-ALL)
Overview
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- Zhejiang University
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Adverse events（AE）
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability, and preliminary efficacy of SYNCAR-100 in patients with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Participants who have signed the informed consent form will undergo screening against the inclusion and exclusion criteria. Eligible participants will receive study drug administration once weekly for a total of four doses, followed by a 1-year safety and efficacy follow-up observation period. After the completion of the study, long-term follow-up may be required for participants to monitor their health and survival status until 15 years post-treatment, or until the occurrence of patient death, loss to follow-up, or withdrawal of consent.
Detailed Description
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal abnormal proliferation and accumulation of lymphoid precursor cells (B or T lineage) in the bone marrow, peripheral blood and other organs. B-cell acute lymphoblastic leukemia (B-ALL) is the more common subtype, accounting for approximately 80% of all cases. For adult patients with relapsed or refractory B-ALL, only about 5-30% can achieve complete remission (CR) following salvage therapy. In addition, among patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), approximately 35% experience disease relapse, with a median overall survival of no more than 6 months; the estimated 1-year, 2-year and 5-year overall survival rates are about 30%, 15% and 10%, respectively. Relapse after allo-HSCT remains a major challenge in the treatment of hematologic malignancies, and there is no effective therapeutic approach recommended by clinical practice guidelines or consensus statements. Therapies such as retransplantation, donor lymphocyte infusion (DLI) and blinatumomab yield overall suboptimal efficacy, creating an urgent unmet medical need for novel and effective therapeutic strategies.
SYNCAR-100 is a next-generation nucleic acid drug candidate developed by Bisheng (Beijing) Biotechnology Co., Ltd. based on circular RNA (circRNA) technology. The safety of SYNCAR-100 will be evaluated by assessing indicators including dose-limiting toxicities (DLT), vital sign measurements, physical examinations, laboratory tests, 12-lead electrocardiography (ECG), peripheral blood B-cell and T-cell levels, and adverse events (AE). The efficacy of SYNCAR-100 in patients with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) will be evaluated by measuring endpoints including the overall response rate (ORR) within 12 weeks, the rate of complete remission with minimal residual disease (MRD)-negativity, duration of response (DOR), progression-free survival (PFS), as well as the ORR within 48 weeks, the rate of patients achieving CR with MRD negativity, DOR, PFS and overall survival (OS). After the completion of the study, long-term follow-up may be required for participants to monitor their health and survival status until 15 years post-treatment, or until the occurrence of patient death, loss to follow-up, or withdrawal of informed consent.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1.Aged 18 to 75 years (inclusive), of any gender.
- •2.Karnofsky Performance Status score ≥
- •3.Estimated life expectancy ≥ 12 weeks.
- •4.Positive CD19 expression on tumor cells confirmed by flow cytometry in bone marrow or peripheral blood.
- •5.Confirmed diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) by bone marrow examination, and meeting one of the following criteria:
- •① Refractory B-ALL: Failure to achieve complete remission (CR) after 2 courses of standard induction chemotherapy, or failure to achieve CR after first-line/multiline salvage chemotherapy.
- •② Relapsed B-ALL: Relapse within 12 months after the first remission, or relapse after first-line/multiline salvage chemotherapy.
- •③Relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT).
- •④ For Philadelphia chromosome-positive (Ph+) patients: At least 2 lines of tyrosine kinase inhibitor (TKI) therapy have failed, or the patient is intolerant to TKI therapy, or the patient harbors the T315I mutation and is resistant to TKIs.
- •6.Proportion of blasts and immature lymphocytes in bone marrow \> 5% confirmed by bone marrow morphologic examination.
Exclusion Criteria
- •1.Isolated extramedullary leukemia or isolated extramedullary relapse.
- •2.Central nervous system (CNS) involvement of leukemia at CNS2 stage.
- •3.A history of other malignant tumors, except for the following: cured non-melanoma skin cancer, carcinoma in situ of the uterine cervix, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, or other malignant tumors with disease-free survival for more than 5 years.
- •4.Positive test results for any of the following infectious diseases: HIV; HCV; HBsAg; positive HBcAb with concurrent positive HBV DNA copy number; TPPA.
- •5.Administration of live or attenuated live vaccines within 4 weeks prior to enrollment.
- •6.Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with tyrosine kinase inhibitor (TKI) therapy within 1 week prior to enrollment.
- •7.Prior receipt of CD19-targeted therapy, CAR-T cell therapy, or other gene-edited T cell therapy.
- •8.Grade ≥2 acute graft-versus-host disease (GVHD) (per Glucksberg criteria) requiring treatment, or extensive chronic GVHD (per Seattle criteria) within 4 weeks prior to enrollment; or patients judged by the investigator to potentially require anti-GVHD therapy during the study period.
- •9.Comorbidities judged by the investigator to require systemic corticosteroid therapy or other immunosuppressive therapy during the study period; or receipt of allogeneic cellular therapy (e.g., donor lymphocyte infusion \[DLI\]) within 4 weeks prior to enrollment.
- •10.Receipt of CNS-directed radiotherapy within 4 weeks prior to enrollment.
Arms & Interventions
SYNCAR-100 Treatment Group
Weekly intravenous (IV) administration for 4 doses. The investigator and sponsor may determine the dosing interval and number of doses for subsequent dose cohorts based on the safety/tolerability, pharmacokinetic parameters, clinical efficacy and prior clinical study experience of the 0.02 mg/kg dose cohort.
Intervention: SYNCAR-100 Injection (Drug)
Outcomes
Primary Outcomes
Adverse events（AE）
Time Frame: within 48 weeks post-dose
Evaluated through laboratory investigations, 12-lead electrocardiography, and vital signs.
Secondary Outcomes
- Minimal Residual Disease（MRD）(within 12 weeks and 48 weeks post-dose)
- Duration of Response（DOR）(within 12 weeks and 48 weeks post-dose)
- Progression-Free Survival（PFS）(within 12 weeks and 48 weeks post-dose)
- Overall Survival（OS）(within 12 weeks and 48 weeks post-dose)
- Pharmacokinetics（PK）(within 4 weeks post-dose)
- Pharmacodynamics（PD）(within 48 weeks post-dose)
- Anti-Drug Antibody（ADA）(within 48 weeks post-dose)
- Overall Response Rate（ORR）(within 12 weeks and 48 weeks post-dose)
Investigators
He Huang
Clinical Professor
Zhejiang University