Natural Killer(NK) Cell Therapy in Acute Myeloid Leukemia

NCT05987696 | Completed Phase 1

• 1 other identifier: IIT2023028
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of iPSC NK cells in patients with relapsed/refractory AML or AML Minimal Residual Disease (MRD).

Conditions

AML, Adult; Minimal Residual Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  28 Days from first dose of iPSC NK cell infusion

• Incidence of subjects with Dose Limiting Toxicities within each dose level cohort

  28 Days from first dose of iPSC NK cell infusion

Secondary Outcomes (6)

• Overall Response Rate(ORR)

  Up to approximately 2 years after last dose of iPSC NK cell infusion

• MRD negative rate

  28 Days from first dose of iPSC NK cell infusion

• Event-free survival

  Up to approximately 2 years after last dose of iPSC NK cell infusion]

• Relapse-free survival

  Up to approximately 2 years after last dose of iPSC NK cell infusion

• Overall survival (OS)

  Up to approximately 2 years after last dose of iPSC NK cell infusion

Study Arms (3)

CD33/CLL1 dual CAR-NK cell

EXPERIMENTAL

CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML

Drug: CD33/CLL1 dual CAR-NK cell; Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Cytarabine

CD33 CAR-NK cell

EXPERIMENTAL

CD33 CAR-NK cell therapy in Adult subjects with r/r AML

Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Cytarabine; Drug: CD33 CAR-NK cell

super NK cell

EXPERIMENTAL

super NK cell therapy in Adult subjects with AML MRD

Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Cytarabine; Drug: super NK cell

Interventions

Fludarabine DRUG

Lympho-conditioning Agent

CD33 CAR-NK cell; CD33/CLL1 dual CAR-NK cell; super NK cell

Cytarabine DRUG

Lympho-conditioning Agent

CD33 CAR-NK cell; CD33/CLL1 dual CAR-NK cell; super NK cell

CD33 CAR-NK cell DRUG

NK cell therapy

CD33 CAR-NK cell

super NK cell DRUG

NK cell therapy

super NK cell

Cyclophosphamid DRUG

Lympho-conditioning Agent

CD33 CAR-NK cell; CD33/CLL1 dual CAR-NK cell; super NK cell

CD33/CLL1 dual CAR-NK cell DRUG

NK cell therapy

CD33/CLL1 dual CAR-NK cell

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form (ICF).
• ≥18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
• Diagnosis of r/r AML (Cohort 1 and 2) or AML MRD (Cohort 3).
• Cohort 1: Both CLL1 and CD33 expression are positive in AML blasts; Cohort 2: The expression of CD33 in AML blast is positive.
• Adequate organ and marrow function, as defined below:
• Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min;
• Total bilirubin (TBIL) ≤ 2 x the ULN;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN;
• Females of childbearing potential must have a negative serum pregnancy test.
• Donor specific antibody (DSA) is negative: MFI \<= 2000.

You may not qualify if:

• Allergic to drug used in this study.
• Subjects received any antitumor therapy as follows, prior to first NK infusion:
• Systemic steroid therapy within 3 days (except physiological replacement therapy);
• Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less;
• Radiotherapy within 4 weeks;
• Donor lymphocyte infusion within 6 weeks;
• Intrathecal treatment within 1 week;
• 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 prior to the first infusion and/or expected to require vaccination from the study period to 12 weeks after the last infusion.
• Active central nervous system Leukemia.
• Acute Promyelocytic Leukemia (APL).
• History of other malignant tumors, except for those who have achieved complete remission more than 5 years after radical treatment without any signs of recurrence.
• Active autoimmune diseases.
• History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.

Sponsors & Collaborators

• Hangzhou Qihan Biotech Co., Ltd.: collaborator
• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

Cyclophosphamide; fludarabine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 14, 2023
• Study Start: July 31, 2023
• Primary Completion: January 17, 2025
• Study Completion: January 17, 2025
• Last Updated: February 11, 2026

Record last verified: 2024-05

Locations

CN (1)