Safety and Efficacy of Allogenic NK Cells in Combination With Chemotherapy in the Treatment of r/r AML After Allo-HSCT

NCT ID: NCT05744440

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2025-05-31

Brief Summary

This is an open label, single-arm, Phase I study to evaluate the efficacy and safety of allogenic natural killer(NK) cells in subjects with refractory or relapsed AML after allogeneic hematopoietic stem cell transplantation(allo-HSCT). A leukapheresis procedure will be performed to manufacture NK cells. Prior to allogenic NK cells infusion subjects will receive chemotherapy with azacitidine.

Detailed Description

This open label, single-arm, Phase I study aims to evaluate the efficacy and safety of allogenic NK cells in subjects with refractory or relapsed AML after allo-HSCT. A leukapheresis procedure will be performed to manufacture NK cells. Prior to allogenic cells infusion subjects will receive chemotherapy with azacitidine. After infusion, the investigators will observe the characteristics of dose limited toxicity (DLT), and determine the maximum tolerable dose(MTD) and recommended phase 2 dose(rp2d) were confirmed. To provide basis for the dosage and treatment plan of cell products in follow-up clinical trials.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

allogenic NK cells

Enrolled patients will receive prespecified dose of allogenic NK cells

Group Type: EXPERIMENTAL

allogenic NK cells

Intervention Type: DRUG

The relapsed/refractory AML after allo-HSCT patients will receive allogenic NK cells infusion up to 2 dose levels (1x10\^7/kg, 5x10\^7/kg) after chemotherapy with azacitidine

Interventions

allogenic NK cells

The relapsed/refractory AML after allo-HSCT patients will receive allogenic NK cells infusion up to 2 dose levels (1x10\^7/kg, 5x10\^7/kg) after chemotherapy with azacitidine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age18-75years old, no gender or race;

2. Expected survival is more than 3 months;

3. Eastern Cooperative Oncology Group (ECOG) score 0-2 points;

4. Diagnosed as AML in accordance with the criteria from Chinese guidelines for the diagnosis and treatment of adult AML (not acute promyelocytic leukemia (APL))(2021) and The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues;

5. Diagnosed as relapsed AML;

6. Measurable lesions meets at least one of the following requirements during screening: (1) Persistent positive MRD or relapse with positive minimal residual disease (MRD) in the bone marrow(BM); (2) Appearance of leukemic blasts in the peripheral blood; (3) ≥5% blasts in the BM; (4) extramedullary relapse;

7. Within 3 days prior to initial treatment, the organ functions meet the following requirements: (1) complete blood cell count: a. Absolute neutrophil counts ≥1.0×109/L and not treated with granulocyte colony stimulating factor(G-CSF) within 7 days; b.Hemoglobin ≥6g/dL(red blood cell; transfusion are permitted); c.Platelet ≥50×109/L(platelet transfusion are permitted); (2) Liver function: alanine transaminase (ALT)/ aspartate aminotransferase(AST) ≤ 3× times upper normal limit(ULN), total bilirubin ≤ 2 times ULN (direct bilirubin ≥ 1.5 times ULN is acceptable for subjects with Gilbert-Meulengracht syndrome); (3)Coagulation function: International standardized ratio (INR) or activated partial thrombin time (APTT) ≤1.5 times ULN; (4)Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30ml/min; (5)Corrected serum calcium ≤14mg/dL (≤3.5mmol/L) or free calcium ≥6.5mg/dL(≥1.6mmol/L); (6)Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%;

8. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

1. Confirmed APL;

2. ≥2 grade persistent nonhematologic toxicity of associated with prior treatment;

3. Patients with grade II-IV graft-versus-host disease (GVHD) requiring the use of immunosuppressive agents ;

4. Systemic steroid therapy exceeding the equivalent of ≥30mg/kg/day of prednisone within 48 hours prior to the first dose of study drug or other immunosuppressive therapies (except for topical and inhaled glucocorticoid therapy, or short-term prophylactic therapy with glucocorticoid) ;

5. Severe cardiovascular and cerebrovascular diseases, including: (1) Some cardiovascular and cerebrovascular diseases (such as congestive heart failure, acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism, etc.) occur within 6 months prior to the first dose of study drug; (2)New York Heart Association (NYHA) Class ≥3 or uncontrolled malignant arrhythmias; (3)The researchers assessed that the subjects with other cardiovascular and cerebrovascular diseases are not suitable for the study;

6. Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis infection, or active pulmonary tuberculosis;

7. History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;

8. Previous or next organ transplant (except for HCT);

9. Women who are pregnant (urine/blood pregnancy test positive) or lactating;

10. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 6 months after enrollment;

11. Any unstable condition potentially imperiling patient safety and compliance;

12. Known alcohol dependence or drug dependence;

13. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Kai Lin Xu，MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kailin Xu, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Xuzhou Medical University

Locations

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Kailin Xu, M.D., Ph.D.

Role: CONTACT

lihmd@163.com

15162166166

Junnian Zheng, M.D., Ph.D

Role: CONTACT

Facility Contacts

Kailin Xu, M.D,Ph.D

Role: primary

lihmd@163.com

15162166166

Other Identifiers

XYFY2022-KL282-01

Identifier Type: -

Identifier Source: org_study_id