Donor Immune Cell Therapy for Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This study aims to introduce a new technology of donor NK cell infusion. NK cells defend against viruses and cancer cells in vivo whereas this effect declines in patiens with tumors. In this study, NK cells will be separated from donated peripheral blood or umbilical cord blood. Eligible NK cells will be infused to patients with Acute myeloid leukemia (AML). This new therapy will probably induce their sustained remission and reduce recurrences.

Detailed Description
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Primary end point: To determine the rate of overall survival at 2 years of Interventional cohort Secondary end point: To determine the cumulative incidence of relapse at 2 years. To determine the rate of disease-free survival at 2 years. Describe the safety and toxicity of donor NK cell infusion. Study Design: This study is a phase I clinical trial. 15 eligible AML patients will be enrolled sequentially to receive detached NK cells product during induction or consolidation therapy. Refractory or relapsed patients and patients who achieved complete remission (CR) after induction therapy are included. They will receive anthracycline-based chemotherapy according to NCCN guidelines. At the same time, Cultured NK cells will be infused into patients after chemotherapy. Anti-allergic therapy and prophylaxis of graft versus host disease (GVHD) will be given before infusion. Treatment effect will be measured and adverse effect will be treated and documented after intervention.

Official Title
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Trial of Donor Immune Cell Therapy for Acute Myeloid Leukemia.

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: infusion of natural killer cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have been diagnosed as acute myeloid leukemia in accordance with Chinese Diagnosis and Treatment Guidelines of AML. Those who achieved CR after chemotherapy are mainly included. Refractory/relapsed AML can also be enrolled. Patients with normal heart function (ejection fraction ≥ 50%), normal liver function(ALT and AST ≤ 2.5 times the upper limit of normal value, bilirubin ≤ 2 times the upper limit of normal value) and normal renal function with blood creatinine ≤ 3.0 mg/dL (≤ 260 µmol /L) can be enrolled. Patients will be required to sign an informed consent. Exclusion Criteria: Patients with severe infection or other malignant tumors. Women during pregnancy or lactation. Other patients deemed unsuitable by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Study Arms: Experimental arm: Cytokine Arm Infusions of Natural Killer (NK) cells
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: immune cell arm<br>Umbilical cord blood or donated peripheral blood of healthy donors were collected and NK cells were cultured. NK cell production will be infused after chemotherapy. | Biological: infusion of natural killer cells<br>* Umbilical cord blood or donated peripheral blood of healthy donors were collected and NK cells were sorted and cultured. NK cell production will be infused after chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hematological response rate | Hematological Complete Remission (HCR): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0x10^9/L; platelet count >100x10^9/L. | up to 2 years, from treatment begining to death | 
| Overall survival | Overall survival (OS) is measured from the date of first infusion of NK cells to the date of death from any cause; patients not known to have died at last follow up are censored on the date they were last known to be alive. | Up to 2 years after beginning treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of relapse | Relapse was defined as the recurrence of above 5%bone marrow blasts and the reappearance of blasts in the blood or the development of extramedullary disease infiltrates at any site. | Up to 2 years after beginning treatment | 
| Disease free survival (DFS) | Disease free survival (DFS) is defined as the time from the date of first infusion of NK cells to the date of relapse or death as a result of any cause. | Up to 2 years after beginning treatment | 
| Incidence of adverse effects | Toxic effects were graded according to the National Cancer Institute's Common Toxicity Criteria. | Up to 2 years after beginning treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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natural killler cell, Acute Myeloid Leukemia