Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases

Phase 2

Terminated

Conditions: Leukemia
Graft Versus Host Disease
Myelodysplastic Syndromes

Registration Number: NCT00450983

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.

Detailed Description: OBJECTIVES:

Primary

* Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells and donor natural killer (NK) cells on the risk of developing grades III-IV acute graft-vs-host disease in patients with leukemia or other hematologic diseases.

Secondary

* Determine the risk for mortality from infection before day 180 in patients treated with this regimen.

* Determine the risk for graft rejection in patients treated with this regimen.

* Determine the risk for life-threatening infections in patients treated with this regimen.

* Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the CD34+ NK/NK-T-enriched graft.

* Determine cytomegalovirus-specific T-cells in product and donor graft.

* Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT).

* Determine the reconstitution of NK function according to time after HSCT.

* Determine the expression of NKG2 ligands of leukemic blasts.

OUTLINE: Patients are stratified according to age (≤ 7 years vs \> 7 years).

* Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation (TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate intrathecally prior to and after donor peripheral blood stem cell (PBSC) transplantation .

* Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising CD34+ purified PBSCs and natural killer (NK) cells on day 0.

Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels; and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if ligands that activate NK cells are expressed.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)	Up to day 100	Count of participants with acute GVHD grades III-IV.

Secondary Outcome Measures

Name	Time	Method
Expression of NKG2 Ligands of Leukemic Blasts	Up to 5 years
Risk for Mortality From Infection Before Day 180	Up to day 180	Count of participant deaths from infection up to day 180.
Risk for Graft Failure	Engraftment documented day +20	Count of participant that had graft failure.
Risk for Life-threatening Infections	Up to day 100	Count of participants with life-threatening infections
Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft	Up to 5 years
Cytomegalovirus-specific T Cells in Product and Donor Graft	Up to 5 years
Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT)	Up to 5 years
Reconstitution of NK Function According to Time After HSCT	Up to 5 years

Trial Locations

Locations (2): Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States