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

NCT05744440 | Unknown Early Phase 1

• 1 other identifier: XYFY2022-KL282-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; allogenic NK cells

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities

  Adverse events assessed according to NCI-CTCAE v5.0 criteria

  1 month

• Objective Response Rate(ORR)

  Assessment of ORR (ORR = complete response(CR) + CRi（CR incomplete blood count recovery）+ PR(partial response)) at 3 months of treatment

  3 months

Secondary Outcomes (2)

• Progression free survival(PFS) Assessment of PFS at month 6,12 Progression free survival(PFS)

  Month 6,12

• Overall Survival(OS)

  Month 6, 12, 18 and 24

Study Arms (1)

allogenic NK cells

EXPERIMENTAL

Enrolled patients will receive prespecified dose of allogenic NK cells

Drug: allogenic NK cells

Interventions

allogenic NK cells 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

allogenic NK cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age18-75years old, no gender or race;
• Expected survival is more than 3 months;
• Eastern Cooperative Oncology Group (ECOG) score 0-2 points;
• 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;
• Diagnosed as relapsed AML;
• 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;
• 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%;
• Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Confirmed APL;
• ≥2 grade persistent nonhematologic toxicity of associated with prior treatment;
• Patients with grade II-IV graft-versus-host disease (GVHD) requiring the use of immunosuppressive agents ;
• 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) ;
• 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;
• 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;
• History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
• Previous or next organ transplant (except for HCT);
• Women who are pregnant (urine/blood pregnancy test positive) or lactating;
• Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 6 months after enrollment;
• Any unstable condition potentially imperiling patient safety and compliance;
• Known alcohol dependence or drug dependence;
• According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Sponsors & Collaborators

• Xuzhou Medical University: lead

Study Sites (1)

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Kailin Xu, M.D., Ph.D.

  Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

15162166166; lihmd@163.com

Junnian Zheng, M.D., Ph.D

CONTACT

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2023
• First Posted: February 27, 2023
• Study Start: March 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: February 27, 2023

Record last verified: 2023-02

Locations

CN (1)