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

Clinical Study on the Safety and Efficacy of QN-023a Targeting CD33 in Acute Myeloid Leukemia

This is an open-label, Phase I study of QN-023a (allogeneic CAR-NK cells targeting CD33) in relapsed/refractory Acute Myeloid Leukemia (AML).

The clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-023a in patients with relapsed/refractory AML,where a "3+3" enrollment schema will be utilized at dose escalation stage. Up to 19 patients will be enrolled.

Study Overview

• Status: Recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Cytarabine; Drug: QN-023a; Drug: VP-16

• Study Type: Interventional
• Enrollment (Anticipated): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Provision of signed and dated informed consent form (ICF)
• ≥18 years old
• Diagnosis of r/r AML
• Subjects with CD33 positive leukemia cells
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate organ function as defined in the protocol
• Donor specific antibody (DSA) to QN-023a: MFI <= 2000

Key Exclusion Criteria:

• Allergic to drug used in this study
• Accept other anti-tumor drugs/therapies within certain time of day 0 (first QN-023a dose infusion), time window and drug defined in the protocol.
• received systemic immunosuppressive therapy within 7 days of day 0, or likely to require systemic immunosuppressive therapy
• Acute Promyelocytic Leukemia (APL)
• Central nervous system Leukemia.
• Uncontrolled, active clinically significant infection
• Clinically significant cardiovascular disease as defined in the protocol
• Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection
• History of central nervous system (CNS) disease such as stroke, epilepsy.
• Females are pregnant or lactating
• Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject

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: QN-023a; QN-023a in adult subjects with r/r AML	Drug: Cyclophosphamid; Lympho-conditioning Agent; Drug: Fludarabine; Lympho-conditioning Agent; Drug: Cytarabine; Lympho-conditioning Agent; Drug: QN-023a; NK cell therapy; Drug: VP-16; Lympho-conditioning Agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of Treatment-Emergent Adverse Events[Safety and Tolerability]	Up to approximately 2 years after last dose of QN-023a
Incidence of dose adjustment or discontinuation due to NK cell toxicities	Up to approximately 2 years after last dose of QN-023a
Incidence of subjects with Dose Limiting Toxicities within each dose level cohort	28 Days from first dose of QN-023a
Determine the maximum tolerated dose (MTD) and RP2D	28 Days from first dose of QN-023a

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the pharmacokinetics (PK) of QN-023a cells in peripheral blood	The PK of QN-023a in peripheral blood will be reported as the relative percentage of product (QN-023a) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points	Up to approximately 2 years after last dose of QN-023a
Overall Response Rate(ORR) of QN-023a in r/r AML	Proportion of subjects who achieve a CR, CRi, CRMRD-, MLFS, or PR, as determined by investigator.	Up to approximately 2 years after last dose of QN-023a
Relapse-free survival (RFS) of QN-023a in r/r AML		Up to approximately 2 years after last dose of QN-023a
Time to Response (TTR) of QN-023a in r/r AML		Up to approximately 2 years after last dose of QN-023a
Event-free survival (EFS) of QN-023a in r/r AML		Up to approximately 2 years after last dose of QN-023a
Overall Survival (OS) of QN-023a in r/r AML		Up to approximately 2 years after last dose of QN-023a
Evaluate the immunogenicity features of QN-023a	The Donor specific antibody (DSA) and T cell receptor (TCR) will be measured.	Up to approximately 2 years after last dose of QN-023a

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Hangzhou Qihan Biotech Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 24, 2022
• Primary Completion (Anticipated): December 24, 2023
• Study Completion (Anticipated): December 24, 2025

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: December 23, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): January 3, 2023
• Last Update Submitted That Met QC Criteria: December 29, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Cytarabine
• Other Study ID Numbers: QN023aM

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