Selection of Allogeneic Hematopoietic Cell Donors Based on KIR and HLA Genotypes

Memorial Sloan Kettering Cancer Center (MSK)

Status: Active, not recruiting

Conditions: Leukemia

Treatments: Genetic: HLA genotyping; Genetic: KIR genotyping

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT02450708

15-059

Details and patient eligibility

About

This study tests whether adding certain genetic factors to the process of picking a stem cell donor can decrease the chances that the patient's leukemia will come back after bone marrow transplantation. Stem cell donors are "matched" based on genes called human leukocyte antigens (HLA).

Currently, donors are selected largely on the basis of HLA gene typing alone. There is published data to show that donors with specific other genes called killer immunoglobulin-like receptors (KIR) may protect AML patients from having their leukemia return after a transplant. In this study, the best HLA matched donors will be tested for the KIR genes. If there is more than 1 donor available, a recommendation will be provided to study doctors as to which donors have potentially favorable KIR genes. The study doctors may or may not choose to use this donor for transplant or not based on his/her own judgment. Transplant care will not change otherwise as a result of this study.

This study is being done to demonstrate that AML patients who have donors with specific KIR and HLA genes will have a better outcome following transplant.

Enrollment: 511 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

RECIPIENT

• Persons of all ages are eligible for this study.
• Patient must have diagnosis of acute myelogenous leukemia (AML) at MSK or a collaborating treating institution. Patients with de novo AML or AML with preceding myelodysplastic syndrome (MDS) are eligible.
• Patient must be a potential candidate for an unrelated transplantation procedure at the time of enrollment even though patient may not be eligible for transplantation in the future due to relapse or presence of co-morbidity(ies).
• An unrelated donor does not need to be identified at the time of enrollment. If an HLA-compatible unrelated donor is not identified for the patient, the patient will be removed from the study.

Exclusion criteria

• Recipients with an available sibling donor matched at HLA-A, HLA-C, and HLA-DRB1 (excluding identical twin siblings).
• Patients for whom post-transplant treatment is planned are not excluded from enrollment.
• Patients with prior allogeneic hematopoietic cell transplantation for AML. Note: Patients who have undergone prior hematopoietic cell transplantation for a diagnosis other than AML are still eligible for this study.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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511 participants in 2 patient groups

For patients with 1 HLA-compatible donor for URD HCT

Experimental group

Description:

For patients with 1 URD: donor KIR genotyping will be performed on the donor. Because donor selection will not depend on KIR/HLA genotyping, completion of donor KIR genotyping is not required prior to transplant.

Treatment:

Genetic: HLA genotyping

For patients with >1 HLA-compatible donor for URD HCT

Experimental group

Description:

For patients with 1 or more donor candidates, KIR genotyping may be performed for up to 5 donors. For patients with HLA-B alleles harboring the Bw4 epitope, KIR3DL1 allele typing will be performed at MSKCC.

Treatment:

Genetic: KIR genotyping

Genetic: HLA genotyping