Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies
ADAPT-HEM
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
1 other identifier
interventional
96
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 2, 2026
CompletedFirst Submitted
Initial submission to the registry
April 5, 2026
CompletedFirst Posted
Study publicly available on registry
April 13, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 14, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 17, 2028
April 13, 2026
April 1, 2026
1 year
April 5, 2026
April 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of dose-limiting toxicities (DLTs) by module and dose level
28 days
Incidence of Grade 3 or higher cytokine release syndrome (CRS)
28 days
Secondary Outcomes (4)
Complete response CR
6 Months
MRD-negative response rate by validated disease-specific assay
90 days
Duration of response (DoR)
24 months
Overall survival (OS)
24 months
Study Arms (8)
Arm A1 CD19/CD22
EXPERIMENTALB-ALL, DLBCL, FL, MCL, PMBCL, CLL/SLL, or Richter transformation with confirmed CD19-positive / CD22-positive disease.
Arm A2 CD19/CD20
EXPERIMENTALB-NHL or CLL/SLL with CD19-positive / CD20-positive disease, especially mature B-cell phenotype or relapse after prior CD19-directed therapy.
Arm B1 BCMA/CD19
EXPERIMENTALMultiple myeloma or plasma cell leukemia with BCMA-positive disease plus evidence of a CD19-positive minor clone, precursor phenotype, or marked clonal heterogeneity.
Arm B2 BCMA/CD38
EXPERIMENTALMultiple myeloma or plasma cell leukemia with BCMA-positive / CD38-positive disease and a plasma-cell-dominant phenotype.
Arm B3 BCMA/ GPRC5D
EXPERIMENTALMultiple myeloma or plasma cell leukemia with BCMA-positive / GPRC5D-positive disease, especially after prior BCMA exposure or with high escape risk.
Arm C1 CD33/CD123
EXPERIMENTALAML, high-risk MDS, or BPDCN with CD33-positive / CD123-positive disease
Arm C2 CD33/CLL1
EXPERIMENTALAML with CD33-positive / CLL1(CLEC12A)-positive disease, particularly stem-cell-rich or measurable residual disease patterns.
Arm D1 CD5/CD7
EXPERIMENTALT-ALL, T-LBL, or peripheral T-cell lymphoma with dual CD5-positive / CD7-positive expression and a feasible fratricide-mitigation plan.
Interventions
Biological: Autologous CD33/CD123 dual-target CAR-T module (simultaneous or planned sequential paired infusion, module-specific) after lymphodepletion.
Biological: Autologous CD33/CLL1 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Biological: Autologous CD19/CD22 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Biological: Autologous CD5/CD7 dual-target CAR-T module (including sequential paired infusion if needed for manufacturing/safety) after lymphodepletion.
Biological: Autologous CD19/CD20 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Biological: Autologous BCMA/CD19 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Biological: Autologous BCMA/CD38 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Biological: Autologous BCMA/GPRC5D dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- \- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Beijing Biotechlead
Study Sites (1)
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Masking Details
- Open-label treatment is necessary because products are individually manufactured, biomarker-matched, and require real-time toxicity management
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2026
First Posted
April 13, 2026
Study Start
March 2, 2026
Primary Completion (Estimated)
March 14, 2027
Study Completion (Estimated)
February 17, 2028
Last Updated
April 13, 2026
Record last verified: 2026-04