CD123-CD16-NK Cells Immunotherapy for AML (CD123-CD16-NK)

February 23, 2025 updated by: Chunji Gao

CD123-Targeted CD16 Antibody-Modified NK Cell Immunotherapy for Refractory/Relapsed Acute Myeloid Leukemia (R/R AML)

The goal of this clinical trial is to evaluate the effectiveness of CD123-CD16 bispecific antibody-modified NK cells in treating patients with CD123-positive relapsed or refractory Acute Myeloid Leukemia (RR AML). It will also assess the safety of this modified NK cell therapy.

The main questions： Does the infusion of CD123-CD16 bispecific antibody-modified NK cells induce remission in RR AML patients? What are the safety and potential adverse effects associated with the administration of these modified NK cells? Researchers will administer CD123-CD16 bispecific antibody-modified NK cells to RR AML patients and compare the outcomes to existing treatment options to determine efficacy and safety.

Participants will:

Undergo lymphocyte-depleting chemotherapy Fludarabine&Cyclophosphamide from day -5 to day -3 before NK cell infusion.

Receive intravenous infusions of modified NK cells at escalating doses:

The first three patients will receive 1×10⁷ cells/kg. The next three patients will receive 2×10⁷ cells/kg. The final three patients will receive 4×10⁷ cells/kg. Have NK cell infusions administered every 96-120 hours for a total of three infusions, with each infusion completed within 10 to 15 minutes.

Undergo dose escalation with subsequent groups only after confirming the safety of the previous dose group.

Have their vital signs (temperature, heart rate, respiratory rate, blood pressure, etc.) monitored before and after each infusion.

Keep baseline data records during NK cell infusions. Participate in follow-up assessments to monitor disease remission and detect any adverse events.

This trial aims to provide new treatment options for RR AML patients by leveraging the targeted cytotoxic effects of CD123-CD16 bispecific antibody-modified NK cells to achieve disease remission.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • 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 Contact Backup

Study Locations

  • China
      • Beijing, China, 100853
        • Recruiting
        • Chinese PLA General Hospital
        • Contact:
        • Contact:
          • Chunji Gao, M.D. & Ph.D.
        • Contact:
          • Yu Jing, M.D. & Ph.D.

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:

  1. Age: Between18 years and 70 years.

  2. Diagnosis and Treatment History:

    Diagnosed with Acute Myeloid Leukemia (AML) in the hospital. Has undergone multiple first-line clinical treatments and has developed resistance to current treatments. Relapse after original induction therapy failure with a predicted survival of more than three months.

  3. CD123 Expression:

    Flow cytometry detection shows CD123-positive AML cells.CD123 expression level is not less than 20%.

  4. Hospital Examination Criteria:

  5. Performance Status:

    ECOG Performance Status score of 0-2 or Karnofsky Performance Status (KPS) score greater than 80.

  6. Donor Availability:
  7. Have a suitable healthy donor and agree to peripheral blood collection.

Exclusion Criteria:

  1. Specific AML Subtype:

    Diagnosed with Acute Promyelocytic Leukemia(APL).

  2. CD123 Expression:

    Flow cytometry shows CD123 negative or CD123 expression level less than 20%.

  3. Prior Treatment Toxicity:

    Persistent non-hematologic toxicity of grade 2 or higher related to previous treatments.

  4. GVHD Requiring Immunosuppression:

    Patients requiring immunosuppressants for grade II-IV acute Graft-Versus-Host Disease (GVHD).

  5. Recent Steroid Treatment:

    Systemic steroid treatment within 7 days prior to first study drug treatment (excluding topical and inhaled corticosteroids or short-term prophylactic steroid treatment).

  6. Severe Cardiovascular and Cerebrovascular Diseases:

    Certain cardiovascular and cerebrovascular diseases within 6 months prior to first dose.

    New York Heart Association (NYHA) classification ≥3 or uncontrolled malignant arrhythmias.Other cardiovascular and cerebrovascular diseases deemed unsuitable by the investigator.

  7. Pregnancy and Lactation:

    Pregnant or breastfeeding women (the safety of this treatment for unborn babies is unknown).

    For female participants, pregnancy must be confirmed negative by serum or urine pregnancy test within 48 hours before infusion.

  8. Infections:

    Active Hepatitis B,Hepatitis C virus infection, Peripheral blood CMV-DNA ≥500 copies/mL, HIV/AIDS infection and any uncontrolled active infection.

  9. Allergic Reactions:

    Allergic to immunotherapy and related drugs.

  10. Neurological Diseases:

Neurological diseases such as neurodegenerative diseases, primary central nervous system tumors/infections, multiple sclerosis, epilepsy, severe peripheral neuropathy, etc.

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
Intervention / Treatment
Experimental: CD123-CD16 bispecific antibody-modified NK cells for the treatment of CD123-positive R/R AML
Patients scheduled to receive CD123-CD16-NK cell infusions undergo lymphocyte-depleting chemotherapy from day -5 to day -3. After completing preconditioning, 48 hours later, patients are intravenously infused with NK cells at a dose of 1×10⁷ cells/kg (100-150 ml volume) within 10 to 15 minutes. Infusions are administered every 96-120 hours for a total of three times. Subsequently, patients receive escalating NK cell doses of 2×10⁷ cells/kg and 4×10⁷ cells/kg. Vital signs (temperature, heart rate, respiratory rate, blood pressure, etc.) are monitored before and after infusion. Baseline data during NK cell infusion are also recorded. For each dose group, only one patient initially receives a single NK cell infusion, followed by a 3-day observation period to ensure safety before proceeding with a second infusion. If no adverse events occur in the initial dose group, the next dose group is infused accordingly, and the process continues similarly.
Drug: Donor-derived CD123-CD16 bispecific antibody-modified NK cells
Patients enrolled sequentially received varying doses of NK cell infusions. The first three patients received 1×10⁷ cells/kg, the next three received 2×10⁷ cells/kg, and the final three received 4×10⁷ cells/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: Bone marrow aspiration assessments are conducted one week after each patient's treatment completion, followed by evaluations at 1 month, 3 months, and 6 months.
Overall Response Rate
Bone marrow aspiration assessments are conducted one week after each patient's treatment completion, followed by evaluations at 1 month, 3 months, and 6 months.
CR
Time Frame: Bone marrow aspiration assessments are conducted one week after each patient's treatment completion, followed by evaluations at 1 month, 3 months, and 6 months.
Complete Remission Rate
Bone marrow aspiration assessments are conducted one week after each patient's treatment completion, followed by evaluations at 1 month, 3 months, and 6 months.
AE
Time Frame: 14 days-28 days after infusion
Adverse events related to cell reinfusion (≥ Grade 3 treatment-related organ toxicity, laboratory tests, and Grade 4 hematologic toxicity, etc.) and number of participants with treatment-related AEs assessed by CTCAE v5.0
14 days-28 days after infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progressive Disease (PD)
Time Frame: 14 days-28 days after infusion
PD parameters: content of CD123+AML cells in peripheral blood ; plasma cytokine levels at various time points;
14 days-28 days after infusion
Stable Disease (SD)
Time Frame: 14 days-28 days after infusion
the condition without significant progression nor significant reduction in AML cells after treatment. The disease is stable, with no significant change in the number of leukemia cells in peripheral blood or bone marrow assessed by IRC.
14 days-28 days after infusion
Progression-free survival (PFS)
Time Frame: through study completion, an average of 6-12moths
the time from cell last infusion to the first assessment of tumor progression, relapse, or death for any reason
through study completion, an average of 6-12moths
Overall survival (OS)
Time Frame: through study completion, an average of 6-12moths
the time from cell last infusion to death for any reason
through study completion, an average of 6-12moths

Collaborators and Investigators

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

Sponsor

Chunji Gao

Collaborators

Chinese PLA General Hospital

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)

February 21, 2025

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

January 7, 2025

First Submitted That Met QC Criteria

February 16, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 23, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S2024-653-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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