Natural Killer(NK) Cell Therapy Targeting CLL1 or CD33 in Acute Myeloid Leukemia

Clinical Study to Evaluate the Safety and Efficacy of iPSC -NK Cells Targeting CLL1 or CD33 in Patients With Relapsed/Refractory AML

This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of CLL1 or CD33 target Chimeric antigen receptor (CAR) -induced pluripotent stem cells derived NK cells in patients with relapsed/refractory AML

Study Overview

• Status: Recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Biological: iPSC-NK cells

Detailed Description

Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed disease in both pediatric and adultpatients.C-type lectin-like molecule-1 and cluster of differentiation antigen 33 has attracted the researchers' attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 or CD33 is an ideal target for AML.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, MD; Phone Number: +8613605714822; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 321000
      • Recruiting
      • the First Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Yongxian Hu; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥18 years old.
• Confirmed diagnosis of r/r AML
• CLL1 or CD33 expression is positive in AML blasts.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.

• Adequate organ and marrow function, as defined below:

  1. Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) ≥ 50 mL/min;
  2. Total bilirubin (TBIL) ≤ 2 x the ULN;
  3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
  4. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN 6.Females of childbearing potential must have a negative serum pregnancy test. 7.Donor specific antibody (DSA) is negative: MFI <= 2000. 8.Provision of signed and dated informed consent form (ICF).

Exclusion Criteria:

• Allergic to drug used in this study.

• Subjects received any antitumor therapy as follows, prior to first NK infusion:

  a. Systemic steroid therapy within 3 days (except physiological replacement therapy):b. Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less; c. Radiotherapy within 4 weeks; d. Donor lmphocyte infusion within 6 weeks: e. Intrathecal treatment within 1 week; f CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;

• History of allogeneic stem cell transplantation.
• Received the vaccine within 4 weeks pror to the first infusion andor expected to reuire vaccination from the study period to 12 weeks ater the last intusion
• Active central nervous system Leukemia.

• Acute Promyelocytic Leukemia (APL).

  .History of other malicnant tumors, except for those who have achieved omplete remission more than 5 years after radical treatment without any sions of recurence9. History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc

• Active autoimmune diseases.
• Serious cardiovascular and cerebrovascular diseases:a. Severe heart rhythm or conduction abnormalities, corrected OT interval (OTc)>480 ms:h, Aute coronay sndrome conestve heat faur. aortic disection-stroke. or other orade 3 or hioher ardiovasular and cerebrovascular events within 6 months orior to firstinfusiorC, New York Heart Association (NYHA) class l or above congestive heart failure or left ventricular eiection fraction (LVEF <50% in olor Doppler echocardiography,d. Hypertension that cannot be controlled by drug.
• Active pulmonary infection: Sp02 90%: Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease
• Uncontrolled bacterial, fungal, or viral infection.Known HlV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection
• Historv of substance abuse.
• Toxicity induced by previous therapy not recovered to s grade 2(NCI-CTCAE 5.0).15. Large suraical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.16. Pregnant/breastfeeding women.17. nvestigator-assessed presence of any medical or social issue that are likely to interfere with study conduct or may cause increased risk to subiect

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: CAR-NK cell therapy in Adult subjects with r/r AML	Biological: iPSC-NK cells; iPSC-NK cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and Tolerability	28 Days from first dose of iPSC NK cell infusion

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Hangzhou Qihanjiyin Biotech Co.,Ltd.
• Investigators: Principal Investigator: He Huang, MD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AML
• Other Study ID Numbers: QH-ZYDC-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