Natural Killer(NK) Cell Therapy in r/r AML

Study Overview
=================
Brief Summary
-----------------
This is an open-label, Phase I study of QN-030a (allogeneic NK cell therapy) in relapse/refractory Acute Myeloid Leukemia (AML). This clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-030a in patients with r/r AML, where a 3+3 enrollment schema will be utilized at dose escalation stage. Up to 18 patients will be enrolled.

Official Title
-----------------
Clinical Study on the Safety and Efficacy of QN-030a in Acute Myeloid Leukemia

Conditions
-----------------
AML, Adult

Intervention / Treatment
-----------------
* Drug: QN-030a
* Drug: Cyclophosphamid
* Drug: Fludarabine
* Drug: Cytarabine
* Drug: VP-16


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Provision of signed and dated informed consent form (ICF) ≥18 years old Diagnosis of r/r AML Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate organ function as defined in the protocol Donor specific antibody (DSA) to QN-030a: 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-030a 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QN-030a<br>QN-030a in Adult subjects with r/r AML | Drug: QN-030a<br>* NK cell therapy<br>Drug: Cyclophosphamid<br>* Lympho-conditioning Agent<br>Drug: Fludarabine<br>* Lympho-conditioning Agent<br>Drug: Cytarabine<br>* Lympho-conditioning Agent<br>Drug: VP-16<br>* Lympho-conditioning Agent<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] |  | Up to approximately 2 years after last dose of QN-030a | 
| Incidence of dose adjustment or discontinuation due to NK cell toxicities |  | Up to approximately 2 years after last dose of QN-030a | 
| Incidence of subjects with Dose Limiting Toxicities within each dose level cohort |  | 28 Days from first dose of QN-030a | 
| Determine the Maximum tolerated dose (MTD) and RP2D |  | 28 Days from first dose of QN-030a | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate(ORR) of QN-030a 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-030a | 
| Relapse-free survival (RFS) of QN-030a in r/r AML |  | Up to approximately 2 years after last dose of QN-030a | 
| Time to Response (TTR) of QN-030a in r/r AML |  | Up to approximately 2 years after last dose of QN-030a | 
| Event-free survival (EFS) of QN-030a in r/r AML |  | Up to approximately 2 years after last dose of QN-030a | 
| Overall Survival (OS) of QN-030a in r/r AML |  | Up to approximately 2 years after last dose of QN-030a | 
| Determination of the pharmacokinetics (PK) of QN-030a cells in peripheral blood | The PK of QN-030a in peripheral blood will be reported as the relative percentage of product (QN-030a) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points | Up to approximately 2 years after last dose of QN-030a | 
| Evaluate the immunogenicity features of QN-030a | The Donor specific antibody (DSA) and T cell receptor (TCR) will be measured. | Up to approximately 2 years after last dose of QN-030a |