Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies (ADAPT-HEM)

April 5, 2026 updated by: Beijing Biotech

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Rationale. Relapse after single-target CAR-T therapy is often driven by antigen down-regulation, lineage plasticity, or pre-existing subclonal heterogeneity. A dual-target framework attempts to preserve depth of response while lowering the probability of escape through loss of one surface antigen. This example therefore uses a master protocol with disease-specific target modules rather than a one-size-fits-all construct. Screening and target selection. All participants undergo central immunophenotyping on bone marrow, peripheral blood, and/or involved tissue within 21 days before enrollment. A module is considered eligible when both antigens are detected on malignant cells by validated flow cytometry or equivalent assay and the anticipated on-target/off-tumor risk is acceptable. If more than one module qualifies, the target selection committee ranks options by disease-specific biology, antigen density, prior antigen-directed therapy, predicted escape risk, and manufacturability.

Treatment schema. Participants undergo leukapheresis, optional bridging therapy, fludarabine/cyclophosphamide lymphodepletion, and infusion of the selected dual-target CAR-T module on Day 0.

Depending on the module, the dual-target strategy may be delivered as a tandem/bicistronic product, compound product, or predefined sequential paired infusion if that is safer or more manufacturable for that antigen pair. Participants are monitored intensively through Day 28, followed for efficacy through Month 24, and may enter long-term gene-modified cell safety follow-up for up to 15 years if required by the final regulatory strategy.

Study Type

Interventional

Enrollment (Estimated)

96

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A1 CD19/CD22
B-ALL, DLBCL, FL, MCL, PMBCL, CLL/SLL, or Richter transformation with confirmed CD19-positive / CD22-positive disease.
Biological: Autologous CD19/CD22 dual-target CAR-T module
Biological: Autologous CD19/CD22 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Experimental: Arm A2 CD19/CD20
B-NHL or CLL/SLL with CD19-positive / CD20-positive disease, especially mature B-cell phenotype or relapse after prior CD19-directed therapy.
Biological: Autologous CD19/CD20 dual-target CAR-T module
Biological: Autologous CD19/CD20 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Experimental: Arm B1 BCMA/CD19
Multiple myeloma or plasma cell leukemia with BCMA-positive disease plus evidence of a CD19-positive minor clone, precursor phenotype, or marked clonal heterogeneity.
Biological: Autologous BCMA/CD19 dual-target CAR-T module
Biological: Autologous BCMA/CD19 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Experimental: Arm B2 BCMA/CD38
Multiple myeloma or plasma cell leukemia with BCMA-positive / CD38-positive disease and a plasma-cell-dominant phenotype.
Biological: Autologous BCMA/CD38 dual-target CAR-T module
Biological: Autologous BCMA/CD38 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Experimental: Arm B3 BCMA/ GPRC5D
Multiple myeloma or plasma cell leukemia with BCMA-positive / GPRC5D-positive disease, especially after prior BCMA exposure or with high escape risk.
Biological: Autologous BCMA/GPRC5D dual-target CAR-T
Biological: Autologous BCMA/GPRC5D dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide
Experimental: Arm C1 CD33/CD123
AML, high-risk MDS, or BPDCN with CD33-positive / CD123-positive disease
Biological: Autologous CD33/CD123 dual-target CAR-T module
Biological: Autologous CD33/CD123 dual-target CAR-T module (simultaneous or planned sequential paired infusion, module-specific) after lymphodepletion.
Experimental: Arm C2 CD33/CLL1
AML with CD33-positive / CLL1(CLEC12A)-positive disease, particularly stem-cell-rich or measurable residual disease patterns.
Biological: Autologous CD33/CLL1 dual-target CAR-T module
Biological: Autologous CD33/CLL1 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Experimental: Arm D1 CD5/CD7
T-ALL, T-LBL, or peripheral T-cell lymphoma with dual CD5-positive / CD7-positive expression and a feasible fratricide-mitigation plan.
Biological: Autologous CD5/CD7 dual-target CAR-T module
Biological: Autologous CD5/CD7 dual-target CAR-T module (including sequential paired infusion if needed for manufacturing/safety) after lymphodepletion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs) by module and dose level
Time Frame: 28 days
28 days
Incidence of Grade 3 or higher cytokine release syndrome (CRS)
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 24 months
24 months
Complete response CR
Time Frame: 6 Months
6 Months
MRD-negative response rate by validated disease-specific assay
Time Frame: 90 days
90 days
Duration of response (DoR)
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

February 17, 2028

Study Registration Dates

First Submitted

April 5, 2026

First Submitted That Met QC Criteria

April 5, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 5, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EBI-ADAPT-HEM-103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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