Natural Killer(NK) Cell Therapy in Acute Myeloid Leukemia

Phase 1

Not yet recruiting

• Conditions: AML, Adult; Minimal Residual Disease
• Interventions: Drug: CD33/CLL1 dual CAR-NK cell; Drug: Cyclophosphamid; Drug: Fludarabine; Drug: super NK cell; Drug: CD33 CAR-NK cell; Drug: Cytarabine

• Registration Number: NCT05987696
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-24
• Status Verified: 2023-08
• Study First Submitted QC: 2023-08-04
• Last Update Submitted: 2023-08-04
• Study Start: 2023-08-10
• Study First Posted: 2023-08-14
• Last Update Posted: 2023-08-14
• Primary Completion: 2026-08-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

1. Provision of signed and dated informed consent form (ICF).

2. ≥18 years old.

3. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.

4. Diagnosis of r/r AML (Cohort 1 and 2) or AML MRD (Cohort 3).

5. Cohort 1: Both CLL1 and CD33 expression are positive in AML blasts; Cohort 2: The expression of CD33 in AML blast is positive.

6. 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;

7. Females of childbearing potential must have a negative serum pregnancy test.

8. Donor specific antibody (DSA) is negative: MFI <= 2000.

Exclusion Criteria

1. Allergic to drug used in this study.

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

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

3. History of allogeneic stem cell transplantation.

4. 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.

5. Active central nervous system Leukemia.

6. Acute Promyelocytic Leukemia (APL).

7. 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.

8. Active autoimmune diseases.

9. History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.

10. Serious cardiovascular and cerebrovascular diseases:

    1. Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms;
    2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to first infusion;
    3. New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) <50% in color Doppler echocardiography;
    4. Hypertension that cannot be controlled by drug.

11. Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease.

12. Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection.

13. History of substance abuse.

14. Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).

15. Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.

16. Pregnant/breastfeeding women.

17. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CD33/CLL1 dual CAR-NK cell	CD33/CLL1 dual CAR-NK cell	CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
super NK cell	super NK cell	super NK cell therapy in Adult subjects with AML MRD
CD33 CAR-NK cell	CD33 CAR-NK cell	CD33 CAR-NK cell therapy in Adult subjects with r/r AML
CD33/CLL1 dual CAR-NK cell	Cyclophosphamid	CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
CD33/CLL1 dual CAR-NK cell	Fludarabine	CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
CD33/CLL1 dual CAR-NK cell	Cytarabine	CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
CD33 CAR-NK cell	Cyclophosphamid	CD33 CAR-NK cell therapy in Adult subjects with r/r AML
CD33 CAR-NK cell	Fludarabine	CD33 CAR-NK cell therapy in Adult subjects with r/r AML
CD33 CAR-NK cell	Cytarabine	CD33 CAR-NK cell therapy in Adult subjects with r/r AML
super NK cell	Cyclophosphamid	super NK cell therapy in Adult subjects with AML MRD
super NK cell	Cytarabine	super NK cell therapy in Adult subjects with AML MRD
super NK cell	Fludarabine	super NK cell therapy in Adult subjects with AML MRD

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood	Up to approximately 2 years after last dose of iPSC NK cell infusion	The PK of iPSC NK in peripheral blood will be reported as the relative percentage of product DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points.

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China