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NCT07523555

Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies

RecruitingPHASE1PHASE2

Study summary

Phase 1/2 umbrella study evaluates biomarker-selected dual-target CAR-T cell modules for adults with relapsed or refractory hematologic malignancies. After central antigen co-expression screening, participants are assigned to the most appropriate active dual-target module: CD19/CD22, CD19/CD20, BCMA/CD19, BCMA/CD38, BCMA/GPRC5D, CD33/CD123, CD33/CLL1, or CD5/CD7. Phase 1 determines safety, dose-limiting toxicities, and the recommended phase 2 dose for each module; phase 2 estimates preliminary antitumor activity, including overall response rate and MRD-negative response. Lymphodepletion with fludarabine/cyclophosphamide precedes infusion. The design is intended to reduce antigen escape by matching disease biology and target co-expression to a rational dual-target strategy.

At a glance

Conditions
Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia, Relapsed/Refractory B-cell Non-Hodgkin Lymphoma or CLL/SLL, Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, High-risk Myelodysplastic Neoplasm, BPDCN; Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia, T-lymphoblastic Lymphoma, Peripheral T-cell Lymphoma
Interventions
Autologous CD19/CD22 dual-target CAR-T module, Autologous CD19/CD20 dual-target CAR-T module, Autologous BCMA/CD19 dual-target CAR-T module, Autologous BCMA/CD38 dual-target CAR-T module, Autologous BCMA/GPRC5D dual-target CAR-T, Autologous CD33/CD123 dual-target CAR-T module, Autologous CD33/CLL1 dual-target CAR-T module, Autologous CD5/CD7 dual-target CAR-T module
Lead sponsor
Beijing Biotech
Target enrollment
96 participants
Age
18 Years75 Years
Sex
ALL
Locations
Peking University Shenzhen Hospital
Registry
View on ClinicalTrials.gov ↗

Eligibility criteria

Inclusion Criteria: * Age 18 to 75 years at the time of consent. * Pathologically or cytologically confirmed eligible disease: B-ALL; B-cell NHL/CLL/SLL; multiple myeloma/plasma cell leukemia; AML/high-risk MDS/BPDCN; or T-ALL/T-LBL/peripheral T-cell lymphoma. * Relapsed or refractory disease after at least 2 prior lines of therapy, or no curative/approved standard option judged appropriate by the investigator. * Central laboratory confirmation that at least one active dual-target module is suitable based on malignant-cell antigen co-expression and safety review. * Measurable or otherwise evaluable disease by disease-specific response criteria. * ECOG performance status 0 to 2. * Adequate organ function: LVEF \>= 45%; creatinine clearance \>= 40 mL/min; AST/ALT \<= 3 x ULN; total bilirubin \<= 1.5 x ULN unless due to Gilbert syndrome; oxygen saturation \>= 92% on room air. * Adequate hematologic reserve unless cytopenia is clearly disease-related. * Ability to undergo leukapheresis and willingness to comply with study procedures and follow-up. * If prior allogeneic HSCT: at least 100 days from transplant, no uncontrolled GVHD, and no systemic immunosuppression above physiologic steroid replacement. * Negative pregnancy test for participants of childbearing potential and agreement to use effective contraception during protocol-defined risk periods. * Written informed consent obtained before any study-specific procedure. Exclusion Criteria: * \- Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection, or clinical sepsis. * Active symptomatic CNS involvement requiring escalating therapy; previously treated/stable CNS disease may be allowed if defined prospectively in the final protocol. * Prior gene-modified cellular therapy within 12 weeks before leukapheresis, or unresolved \>= Grade 3 toxicity from prior anticancer therapy * Need for urgent cytoreduction such that manufacturing delay would create unacceptable clinical risk. * Active autoimmune disease requiring systemic immunosuppression, except limited replacement-dose steroids or protocol-permitted topical/inhaled therapy. * Prior solid organ transplant. * Clinically significant cardiovascular disease, uncontrolled arrhythmia, decompensated heart failure, myocardial infarction within 6 months, or recent stroke within 6 months. * Uncontrolled HIV, HBV, or HCV viremia. * Pregnancy or breastfeeding. * Another active malignancy requiring systemic therapy, unless low-risk and definitively treated per protocol-defined exceptions. * Known hypersensitivity to fludarabine, cyclophosphamide, or critical product excipients. * Inability to manufacture a releaseable CAR-T product or failure to meet module-specific product-release criteria. * Any medical, psychiatric, or social condition that, in the investigator's judgment, would increase risk, impair compliance, or confound interpretation of study results.