Overview

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

Status:
Recruiting

Trial end date:
2025-05-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Early Phase 1

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Xuzhou Medical University

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.