Safety and Efficacy Study of Donor Natural Killer Cells Given After Haploidentical Hematopoietic Cell Transplantation

Study Overview
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Brief Summary
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The protocol treatment is to evaluate clinical effects of donor-derived natural killer cells that are given after HLA-mismatched hematopoietic cell transplantation.

Detailed Description
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Those patients with acute leukemia, which is not responding to coventional chemotherapy, will be treated. The clinical effects will be evaulated in terms of safety (side effects) and anti-leukemia effect.

Official Title
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HLA-Haploidentical Hematopoietic Cell Transplantation and Subsequent Donor Natural Killer Cell Infusion in Refractory Acute Leukemia - A Phase 1-2a STUDY

Conditions
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Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: donor natural killer cell infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute leukemia, which are refractory to standard treatment. Patients should be 17 years of age or older. The performance status of the patients should be 70 or over by Karnofsky scale. Patients should not have excessive hepatic dysfunction (bilirubin less than 3.0 mg/dl, AST less than 5 times the upper normal limit). Patients should not have excessive renal dysfunction (creatinine less than 3.0 mg/dl). Patients should not have clinically-evident cardiac or pulmonary dysfunction. Patients and donors must sign informed consent. Exclusion Criteria: Patients who are pregnant or lactating are not eligible.

Ages Eligible for Study
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Minimum Age: 17 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: donor natural killer cell infusion|Donor NK cells will be generated at the GCP laboratory at Asan Institute of Life Science by a team from Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology. The patients will receive donor NK cell infusion (DNKI) around on days 6 and 9 (generated from the first collection), and around on days 13 and 20 (generated from the second collection). For DNKI to be given on days 6 and 9, a 3-patient cohort each will receive escalating dose of 2x10e7/kg, 5x10e7/kg, 1x10e8/kg, and 1-4 x10e8 cells. The dose of DNKI to be given on days 13 and 20 will be 1-4 x10e8/kg.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence and severity of side effects of donor natural killer cell infusion |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anti-leukemia effect of donor natural killer cell infusion |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myelogenous leukemia, acute lymphoblastic leukemia, donor natural killer cells, HLA-haploidentical hematopoietic cell transplantation