Functionally Optimized CD33 CAR-T Cell Therapy Targeting Recurrent/Refractory Acute Myeloid Leukemia

April 19, 2026 updated by: Qi deng

Clinical Study on the Efficacy and Safety of Functionally Optimized CD33 CAR-T Cells (FO33 CAR-T) Therapy Targeting CD33-Positive Recurrent/Refractory Acute Myeloid Leukemia

Relapsed/refractory acute myeloid leukemia (R/R AML) currently lacks effective CAR-T therapeutic agents due to the absence of tumor-specific target antigens. Most AML-associated antigens are expressed on normal hematopoietic stem/progenitor cells (HSPCs) and healthy tissues, increasing the risk of on-target off-tumor toxicity and non-neoplastic toxicity. CD33 is present on leukemic cells in over 80% of AML patients. Compared with CLL-1, CD123 and other targets, CD33 exhibits higher expression across diverse AML subtypes, reducing the risk of treatment failure and relapse caused by antigen escape and thus serving as an ideal therapeutic target for AML. However, conventional CD33-targeted CAR-T cells demonstrate suboptimal efficacy in clinical trials, accompanied by significant toxicity and inadequate in vivo expansion. To further investigate the safety and efficacy of CAR-T therapy for AML, our center has initiated a clinical trial of functionally optimized CD33 CAR-T (FO33 CAR-T) cells for R/R AML. We constructed a lentiviral CAR vector containing the CD33-targeting scFv, 4-1BB, and CD3ζ, followed by insertion of adjuvant molecule X. FO33 CAR-T cells showed superior cytotoxicity against AML cell lines and enhanced biological activity compared with conventional CD33 CAR-T cells, and exerted safe and effective antitumor effects in preclinical models. This single-center, open-label, prospective clinical trial aims to evaluate the safety and efficacy of FO33 CAR-T cells in patients with R/R AML, as well as to characterize the pharmacokinetic and pharmacodynamic (PK/PD) profiles of this therapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects diagnosed with refractory/recurrent acute myeloid leukemia (excluding M3) who meet any of the following criteria:

    1. Relapse: Recurrence of leukemia cells in peripheral blood or ≥5% blast cells in bone marrow after complete remission (CR) of AML (excluding other causes such as bone marrow regeneration following consolidation chemotherapy), or extramedullary leukemia infiltration.
    2. Refractory: First-time cases unresponsive to two cycles of standard therapy; relapse within 12 months after consolidation therapy following CR; relapse after 12 months without response to conventional chemotherapy; two or more relapses; persistent extramedullary leukemia.
  • During enrollment screening, bone marrow flow cytometry must demonstrate a CD33+ expression rate of ≥80% in leukemia cells and/or pathological immunohistochemical confirmation of CD33+ extramedullary lesions.
  • Estimated survival duration exceeding 3 months as of the date of informed consent signing.
  • Participants with Eastern Cooperative Oncology Group (ECOG) physical status scores ranging from 0 to 2.
  • Age range of 14 years ≤ ≤ 75 years, inclusive, with no gender restriction.
  • Hemoglobin (HGB) level ≥70 g/L with transfusion capability.

  • Liver/kidney function and cardiopulmonary function meeting the following criteria:

    1. Creatinine ≤1.5×ULN;
    2. Left ventricular ejection fraction ≥50%;
    3. Blood oxygen saturation>90%;
    4. Total bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN.
  • Acceptance of autologous CART cells with peripheral blood tumor burden ≤ 30%;
  • The subject or guardian understands and signs the informed consent form.

Exclusion Criteria:

  • Presence of one of the following cardiac criteria:

    1. Atrial fibrillation;
    2. Myocardial infarction (MI) within the past 12 months;
    3. Prolonged QT syndrome or secondary QT prolongation as determined by the investigator;
    4. Echocardiographic left ventricular systolic fraction (LVSF) <30% or left ventricular ejection fraction (LVEF) <50%;
    5. Clinically significant pericardial effusion; New York Heart Association (NYHA) class III or IV heart failure (confirmed by echocardiography within 12 months after treatment).
  • Active graft-versus-host disease (GVHD).
  • History of severe pulmonary dysfunction.
  • Concurrent other progressive malignancies.
  • Concurrent severe or persistent infections that cannot be effectively controlled.
  • Concurrent severe autoimmune diseases or congenital immunodeficiency.
  • Active hepatitis (HBV-DNA ≥ 500 IU/ml with abnormal liver function or HCV antibody [HCV-Ab] positivity, HCV-RNA exceeding the detection limit of analytical methods with abnormal liver function).
  • Human immunodeficiency virus (HIV) infection or syphilis infection.
  • History of severe allergic reactions to biological products (including antibiotics).
  • Presence of central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, or cerebellar diseases.
  • Female patients in pregnancy or lactation, or planning pregnancy within 12 months.
  • Situations where investigators consider may increase subject risk or interfere with trial outcomes.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Functionally optimized CD33 CAR-T
Based on previously reported clinical data regarding the safety and efficacy of CAR-T cell infusion in AML trials, as well as ethical considerations for benefit-risk assessment aimed at protecting subject safety, the initial infusion doses in this trial were set as follows: Dose 1: 0.5×10⁶ (±30%) CAR-T cells/kg, Dose 2: 1×10⁶ (±30%) CAR-T cells/kg, and Dose 3: 2×10⁶ (±30%) CAR-T cells/kg.
Biological: Functionally optimized CD33 CAR-T
Functionally optimized CD33 CAR-T intravenous infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluate the Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
Time Frame: up to one month after the CAR-T infusion
the incidence and severity of immune therapy related toxic reactions (irAEs)
up to one month after the CAR-T infusion
Evaluate the Complete Response rate of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
Time Frame: one month and three month after the CAR-T infusion
Complete Response rate on M1 and M3
one month and three month after the CAR-T infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cell pharmacokinetics Dynamic indicators
Time Frame: Day7, Day10, Day14, Day28 after the CAR-T infusion
CAR-T/T% by flow cytometry
Day7, Day10, Day14, Day28 after the CAR-T infusion
long-term efficacy
Time Frame: up to one year after the CAR-T infusion
Overall Survival
up to one year after the CAR-T infusion

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Qi deng

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 20, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XBAP2025-13

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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