Adaptive dual-target CAR-T therapy for relapsed or refractory blood cancers
A Phase 1/2, Open-Label, Nonrandomized, Multi-arm Umbrella Study of Biomarker-Selected Dual-Target CAR-T Cell Modules in Adults With Relapsed or Refractory Hematologic Malignancies
This trial will test whether matching a patient's cancer markers to one of several dual-target CAR-T therapies can work and be safe for adults whose blood cancer has come back or not responded.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 96 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07523555 on ClinicalTrials.gov |
What this trial studies
This phase 1/2 master protocol uses central immunophenotyping to match adults with relapsed or refractory hematologic malignancies to a biomarker-selected dual-target CAR-T module (for example CD19/CD22, CD19/CD20, BCMA/CD38, CD33/CD123, or CD5/CD7). Participants undergo leukapheresis, optional bridging therapy, fludarabine/cyclophosphamide lymphodepletion, and infusion of the selected autologous dual-target CAR-T product delivered as a tandem, bicistronic, compound, or sequential infusion depending on the antigen pair. Phase 1 identifies safety, dose-limiting toxicities, and the recommended phase 2 dose for each module, while phase 2 estimates preliminary antitumor activity including overall response rate and MRD-negative responses. Intensive monitoring through the first 28 days and scheduled longer-term follow-up will capture adverse events, response durability, and signs of antigen escape.
Who should consider this trial
Good fit: Adults aged 18–75 with relapsed or refractory B- or T-cell leukemias, lymphomas, multiple myeloma/plasma cell leukemia, AML/high-risk MDS, or BPDCN after prior therapies, whose tumor cells co-express the antigen pair required for at least one active module and who meet organ-function and performance criteria are ideal candidates.
Not a fit: Patients whose malignant cells do not co-express both antigens for any available module, or who have inadequate organ function or uncontrolled comorbidity preventing leukapheresis or lymphodepletion, are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this approach could lower relapse from antigen loss and produce deeper, longer-lasting remissions across multiple blood cancers.
How similar studies have performed: Smaller dual-target CAR-T studies (for example CD19/CD22 and BCMA-containing constructs) have shown promising activity in specific diseases, but this biomarker-selected master-protocol approach is novel and broader in scope.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Shenzhen, Guangdong
- Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: shan S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.