Selecting a Favorable KIR Donor in Unrelated HCT for AML

Study Overview
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Brief Summary
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Donors with favorable KIR B haplotype gene content have yielded reduced relapse risk and improved leukemia free survival (LFS) in retrospective analyses of unrelated donor (URD) hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML). Specifically, donors with more KIR B gene content and those who are homozygous for the centromeric (Cen) B haplotype genes (as opposed to the telomeric (Tel) genes confer the most protective effect. This study proposes to prospectively test and validate the utility and effectiveness of further informing URD identification and selection by KIR genotyping as a supplement to HLA matching and the other variables known or suspected to indicate the best URD for a patient. Hypotheses: Favorable KIR donors will improve protection against relapse and improve leukemia free survival (LFS) after URD HCT for AML. Directed study procedures for rapid KIR genotyping and reporting to searching Transplant Centers (TC) can inform donor search and selection without delay in donor availability for HCT.

Detailed Description
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Transplant Centers will select the best HLA matched, and as appropriate, preferred KIR donor.

Official Title
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KIR Genotyping for Unrelated Donor (URD) Selection Prior to Hematopoietic Cell Transplantation (HCT) for AML: Selecting a Favorable KIR Donor

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Other: KIR genotype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with acute myeloid leukemia (AML) undergoing screening for potential URD HCT Potential URD undergoing screening to provide a HCT graft to a patient with acute myeloid leukemia (AML) at a participating institution Provides written consent Exclusion Criteria: Transplant Centers will select the best HLA matched, and as appropriate, preferred KIR donor. In situations where the preferred (best > better > neutral) KIR donor is not selected in favor of a less favorable KIR genotype donor, the center will report one or more defined reasons (donor age; gender; parity; CMV status; ABO status; availability/logistics; other) for the choice (among equivalently HLA matched donors).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unrelated Donor Transplant Patients<br>Patients with acute myeloid leukemia who have received KIR genotype from an unrelated donor transplant. | Other: KIR genotype<br>* KIR genotype data from unrelated donor are collected<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Relapse | To measure the impact of donor selection for KIR genotype in allogeneic URD HCT for AML on cumulative incidence of relapse. We will determine a quantitative estimate of the likelihood of better KIR donors identified with routine, non-directed donor selection along with KIR genotyping data. The observed incidence of success in a better KIR donor identified within 8 weeks will be compared to the original donor genotype expected frequencies identified in our retrospective genotyping of 1086 donors selected for AML transplants. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Relapse-Free Survival |  | 2 Years | 
| Overall Survival |  | 2 Years | 
| Incidence of Engraftment |  | 2 Years | 
| Incidence of Graft Versus Host Disease |  | 2 Years | 
| Incidence of Transplant Related Mortality | Number of patients who died within 2 years of transplant. | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myelogenous leukemia, hematopoietic cell transplantation, unrelated donor