Killer Immunoglobulin-like Receptor (KIR) Incompatible Unrelated Donor Hematopoietic Cell Transplantation (SCT) for AML With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory and Relapsed Acute Myelogenous Leukemia (AML) in Children: A Children's Oncology Group (COG) Study
OBJECTIVES:
- To define the relationship between the status of donor NK-cell receptor and patient
outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD)
and umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) in young
patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3 internal tandem
duplication allelic ratio (High-FLT3-ITD AR), or refractory or relapsed acute
myelogenous leukemia.
- To correlate the relationships between factors affecting NK receptor status and
clinical events.
- To assess NK-cell development after URD and UCB HCT in patients with poor prognosis
AML.
- To evaluate NK-cell reconstitution and receptor-acquisition pattern in these patients.
OUTLINE: This is a multicenter study.
- Preparative regimen: Patients receive 1 of the following regimens:
- Hematopoietic stem cell transplantation (SCT): Patients receive busulfan IV every
6 hours on days -9 to -6, high-dose cyclophosphamide IV over 1 hour on days -5 to
-2, anti-thymocyte globulin IV once or twice daily over 4 hours on days -3 to -1,
and methylprednisolone IV on days -3 to -1.
- Umbilical cord blood (UCB) transplantation: Conditioning regimen, infusion
procedures, and post-transplant immunoprophylaxis for patients with an UCB donor
are according to institutional guidelines and standards.
- Allogeneic hematopoietic stem cell transplantation (SCT) or umbilical cord blood (UCB)
transplant: Patients undergo allogeneic SCT or UCB transplant on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine or tacrolimus
IV or orally beginning on day -2 and continuing until day 50, followed by a taper until
week 24. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Blood samples will be collected periodically from both patients and donors for studies of
natural killer cells in support of the study objectives.
After completion of study treatment, patients are followed every 6 months for 2 years and
then annually for 3 years.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival
OS will be estimated using Kaplan-Meier methods. For the primary endpoint of overall survival, there should be similar power for other covariates including recovery of NK cell number, acquisition of donor pattern of KIR expression, and acquisition of activating receptors and co-receptors, because the distribution of patients in each risk category is similar (assume ~50% of the patients reconstitute by 6 months after SCT)
Up to 5 years after SCT
No
Stella M. Davies, MBBS, PhD
Study Chair
Children's Hospital Medical Center, Cincinnati
United States: Federal Government
AAML05P1
NCT00553202
January 2008
Name | Location |
---|---|
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
CCOP - Scott and White Hospital | Temple, Texas 76508 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Mercy Hospital | Kansas City, Missouri 64108 |
Nemours Children's Clinic | Jacksonville, Florida 32207 |
All Children's Hospital | St. Petersburg, Florida 33701 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
Children's Hospital Central California | Madera, California 93638-8762 |
Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
Midwest Children's Cancer Center at Children's Hospital of Wisconsin | Milwaukee, Wisconsin 53226 |
Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
Nemours Children's Clinic - Orlando | Orlando, Florida 32806 |
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus | Atlanta, Georgia 30322 |
Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
CCOP - Nevada Cancer Research Foundation | Las Vegas, Nevada 89109-2306 |
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Dayton Children's - Dayton | Dayton, Ohio 45404-1815 |
Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
Penn State Children's Hospital | Hershey, Pennsylvania 17033-0850 |
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
Virginia Commonwealth University Massey Cancer Center | Richmond, Virginia 23298-0037 |
Riley's Children Cancer Center at Riley Hospital for Children | Indianapolis, Indiana 46202-5225 |
UAB Comprehensive Cancer Center | Birmingham, Alabama 35294 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |