Selecting a Favorable KIR Donor in Unrelated HCT for AML

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

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:

1. Favorable KIR donors will improve protection against relapse and improve leukemia free survival (LFS) after URD HCT for AML.
2. 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.

Study Overview

• Status: Completed
• Conditions: Acute Myelogenous Leukemia
• Intervention / Treatment: Other: KIR genotype

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 506
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Scottsdale
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • New York Presbyterian Weill Cornell Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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
Overall Survival		2 Years
Incidence of Relapse-Free 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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel Weisdorf, M.D., Masonic Cancer Center, University of Minnesota

Publications and helpful links

General Publications

• Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Marsh SG, Spellman S, Haagenson MD, Saeturn K, Ladner M, Trachtenberg E, Parham P, Miller JS. Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. J Immunol. 2014 May 15;192(10):4592-600. doi: 10.4049/jimmunol.1302517. Epub 2014 Apr 18.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 1, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: hematopoietic cell transplantation; acute myelogenous leukemia; unrelated donor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2010LSUC043; MT2010-06 (Other Identifier: Blood and Marrow Transplantation Program); P01CA111412 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No