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

Primary Purpose

AML, Adult

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
QN-023a
Cyclophosphamid
Fludarabine
Cytarabine
VP-16
Sponsored by
Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AML, Adult

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The first affiliated hospital of medical college of zhejiang universityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

QN-023a

Arm Description

QN-023a in adult subjects with r/r AML

Outcomes

Primary Outcome Measures

Incidence and severity of Treatment-Emergent Adverse Events[Safety and Tolerability]
Incidence of dose adjustment or discontinuation due to NK cell toxicities
Incidence of subjects with Dose Limiting Toxicities within each dose level cohort
Determine the maximum tolerated dose (MTD) and RP2D

Secondary Outcome Measures

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.
Relapse-free survival (RFS) of QN-023a in r/r AML
Time to Response (TTR) of QN-023a in r/r AML
Event-free survival (EFS) of QN-023a in r/r AML
Overall Survival (OS) of QN-023a in r/r AML
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
Evaluate the immunogenicity features of QN-023a
The Donor specific antibody (DSA) and T cell receptor (TCR) will be measured.

Full Information

First Posted
December 13, 2022
Last Updated
December 29, 2022
Sponsor
Zhejiang University
Collaborators
Hangzhou Qihan Biotech Co.,Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05665075
Brief Title
Natural Killer (NK) Cell Therapy Targeting CD33 in Acute Myeloid Leukemia
Official Title
Clinical Study on the Safety and Efficacy of QN-023a Targeting CD33 in Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 24, 2022 (Anticipated)
Primary Completion Date
December 24, 2023 (Anticipated)
Study Completion Date
December 24, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Hangzhou Qihan Biotech Co.,Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AML, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
QN-023a
Arm Type
Experimental
Arm Description
QN-023a in adult subjects with r/r AML
Intervention Type
Drug
Intervention Name(s)
QN-023a
Intervention Description
NK cell therapy
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamid
Intervention Description
Lympho-conditioning Agent
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Lympho-conditioning Agent
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Lympho-conditioning Agent
Intervention Type
Drug
Intervention Name(s)
VP-16
Intervention Description
Lympho-conditioning Agent
Primary Outcome Measure Information:
Title
Incidence and severity of Treatment-Emergent Adverse Events[Safety and Tolerability]
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Incidence of dose adjustment or discontinuation due to NK cell toxicities
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Incidence of subjects with Dose Limiting Toxicities within each dose level cohort
Time Frame
28 Days from first dose of QN-023a
Title
Determine the maximum tolerated dose (MTD) and RP2D
Time Frame
28 Days from first dose of QN-023a
Secondary Outcome Measure Information:
Title
Overall Response Rate(ORR) of QN-023a in r/r AML
Description
Proportion of subjects who achieve a CR, CRi, CRMRD-, MLFS, or PR, as determined by investigator.
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Relapse-free survival (RFS) of QN-023a in r/r AML
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Time to Response (TTR) of QN-023a in r/r AML
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Event-free survival (EFS) of QN-023a in r/r AML
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Overall Survival (OS) of QN-023a in r/r AML
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Determination of the pharmacokinetics (PK) of QN-023a cells in peripheral blood
Description
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
Time Frame
Up to approximately 2 years after last dose of QN-023a
Title
Evaluate the immunogenicity features of QN-023a
Description
The Donor specific antibody (DSA) and T cell receptor (TCR) will be measured.
Time Frame
Up to approximately 2 years after last dose of QN-023a

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, PhD
Phone
86-15957162012
Email
huyongxian2000@aliyun.com
Facility Information:
Facility Name
The first affiliated hospital of medical college of zhejiang university
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, MD
Phone
86-13605714822
Email
hehuangyu@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

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

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