Donor Stem Cell Transplant in Treating Young Patients With Acute Myeloid Leukemia With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory or Relapsed Acute Myelogenous Leukemia
- Conditions
- Leukemia
- Interventions
- Biological: anti-thymocyte globulinOther: laboratory biomarker analysisOther: pharmacological studyProcedure: allogeneic bone marrow transplantationProcedure: allogeneic hematopoietic stem cell transplantation
- Registration Number
- NCT00553202
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may stop this from happening.
PURPOSE: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting leukemia. Bone marrow donors can be selected based on the type of NK cells they have, specifically the killer immunoglobulin receptor (KIR) type. This study provides information on KIR type from potential donors, which can be used in selecting the bone marrow donor. This phase II trial of unrelated donor stem cell transplant in patients with high risk AML (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of the patients and potential donors will be available to the treating transplant physician at the time of donor selection.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 158
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy and allogeneic SCT) laboratory biomarker analysis 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) allogeneic bone marrow transplantation 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) allogeneic hematopoietic stem cell transplantation 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) anti-thymocyte globulin 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) pharmacological study 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) busulfan 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) cyclophosphamide 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) cyclosporine 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) methotrexate 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) methylprednisolone 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives Treatment (chemotherapy and allogeneic SCT) tacrolimus 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. Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0. 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 pharmacological study objectives
- Primary Outcome Measures
Name Time Method Overall Survival (OS) At 5 years from HSCT date OS - Time from HSCT until death
Cumulative Incidence of NK Cell Reconstitution At 5 years from HSCT date Cumulative incidence of successful reconstitution to donor level is calculated.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (52)
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
🇺🇸Atlanta, Georgia, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
🇺🇸Long Beach, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Lucille P. Markey Cancer Center at University of Kentucky
🇺🇸Lexington, Kentucky, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Dayton Children's - Dayton
🇺🇸Dayton, Ohio, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Children's and Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Riley's Children Cancer Center at Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States