A Phase I Single-arm Clinical Study of Donor NK Cells Infusion Combined with Low-dose Interleukin-2 in the Treatment of Acute Myeloid Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation.

This is a single-centre, single-arm, open-label, early clinical study to evaluate the safety, tolerability and preliminary efficacy of donor NK cells injection combined with low-dose interleukin-2 in the treatment of acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia (AML) Relapse; NK Cell
• Intervention / Treatment: Drug: NK cell

Detailed Description

This is a dose-escalation study of non-genetically modified natural killer cells derived from a healthy donor. The relapsed AML patients after allo-HSCT will receive donor NK cells injection s followed by low-dose interleukin-2. No graft-versus-host disease (GVHD) prevention will be conducted before or after infusion. Dose-limiting toxicity, incidence of adverse events, disease response and PK/PD will be detected post-infusion.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yujun Dong, Docter; Phone Number: 8683575680; Email: dongy@hsc.pku.edu.cn
• Study Contact Backup: Name: Bingjie Wang; Email: wbj880202@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
      • Contact: Yujun Dong; Phone Number: +86 18210264969; Email: dongy@hsc.pku.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Age ≥ 18 years old, no gender or race; 2.Expected survival period ≥ 3 months; 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; 4.The diagnosis of AML who received allo-HSCT, and met the following criteria: A. Diagnostic criteria for relapsed AML: after complete remission (CR), leukemia cells reappeared in peripheral blood or blast cells in bone marrow ≥ 5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; B. Minimal Residual Disease (MRD) positive only or relapse: Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment; C. Degree II and above acute graft-versus-host disease did not occur after transplantation; D. Available allogeneic hematopoietic stem cell transplant donors. 5. Adequate organ function: A. Liver function: ALT≤3×ULN, AST≤3×ULN, total bilirubin≤2×ULN; B. Coagulation function: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5×ULN; C. Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30mL/min; D. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 45%; 6. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.; 7. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• 1. Central nervous system involved; 2. Patients who received the following anti-tumor therapies prior to infusion: A. Systemic use of hormones within 3 days prior to infusion (except for patients with inhaled corticosteroids); B. Systemic anti-tumor therapy within 2 weeks or within 5 drug half-lives (whichever is shorter); C. Radiotherapy within 4 weeks; D. DLI within 6 weeks; E. Intrathecal injection within 1 week; F. Received CAR-T, CAR-NK or other modified cell therapy within 6 months; 3. Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: HBV, HCV, HIV, syphilis infection, or active pulmonary tuberculosis.

  4. History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; 5. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment; 6. Women who are pregnant (urine/blood pregnancy test positive) or lactating; 7. Suffering from a serious autoimmune disease or immunodeficiency disease; 8. Known alcohol dependence or drug dependence; 9. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NK cell treatment in AML replase after HSCT; The relapsed AML patients will receive donor NK cells injections for a total dose of twice per 2 weeks up to 3 dose levels (1.0×108 cells/dose，5.0×108 cells/dose，2.0×109 cells/dose), followed by low-dose interleukin-2 (1mIU ih, Qd) for 28 days.	Drug: NK cell; Drug: Donor NK cells injection is a non-genetically modified natural killer cells therapy derived from a healthy donor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLTs)	Dose limiting toxicities (DLTs)	1 month
Treatment-related adverse events	Treatment-related adverse events	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with minimal-residual disease (MRD) negative response		3 months
Complete response (CR)	Complete response (CR)	3 months
Peak levels of donor NK cells (maximum concentration or Cmax)		3 months

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Yujun Dong, Docter, Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: relapse; AML; NK cell; allogeneic hematopoietic stem cell transplantation.
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence
• Other Study ID Numbers: PKUFH JDCO2

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