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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00553202
Recruitment Status : Active, not recruiting
First Posted : November 5, 2007
Results First Posted : February 24, 2017
Last Update Posted : February 24, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Leukemia Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Drug: methylprednisolone Drug: tacrolimus Other: laboratory biomarker analysis Other: pharmacological study Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Phase 2

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 158 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2008
Actual Primary Completion Date : June 2016

Arm Intervention/treatment
Experimental: Treatment (chemotherapy and allogeneic 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.

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

Biological: anti-thymocyte globulin
Given IV
Other Names:
  • Rabbit ATG
  • RATG-Rabbit
  • Antithymocyte Globulin
  • Thymoglobulin
  • NSC #720095
Drug: busulfan
Given IV
Other Names:
  • Busulfex
  • NSC #750
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cyclosporine
Given IV or orally
Other Names:
  • CYA
  • Sandimmune
  • Neoral
  • Gengraf
  • NSC #290193
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #000740
Drug: methylprednisolone
Given IV
Other Names:
  • Solu-Medrol
  • A-Methapred
  • Medrol
  • NSC #19987
Drug: tacrolimus
Given IV
Other Names:
  • FK-506
  • Prograf
  • NSC #717865
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Procedure: allogeneic bone marrow transplantation
allogeneic bone marrow transplantation
Other Names:
  • bone marrow therapy
  • allogeneic
  • allogenic
  • transplantation
  • allogeneic bone marrow
  • allogenic bone marrow
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic SCT

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: At 5 years from HSCT date ]
    OS - Time from HSCT until death

  2. Cumulative Incidence of NK Cell Reconstitution [ Time Frame: At 5 years from HSCT date ]
    Cumulative incidence of successful reconstitution to donor level is calculated.

Other Outcome Measures:
  1. Disease-free Survival [ Time Frame: From the date of SCT to the date of relapse, the date of death, or the date of last follow-up, whichever occurs first ]
    The cumulative incidence of relapse or death after SCT will be calculated by considering relapse and death due to other causes as competing events.

  2. Acute and Chronic Graft-versus-host Disease [ Time Frame: Up to 5 years ]
    Acute and chronic GVHD will be summarized.

  3. Time to the Donor-specific NK-cell Receptor Expression [ Time Frame: Up to 42 days after SCT ]
    The presence of donor cells is demonstrated by the detection of informative variable-number tandem-repeat polymorphisms or by fluorescent in situ hybridization with a Y-chromosome-specific probe in cases of sex-mismatched transplants. Independent variables that will be examined include donor-recipient KIR mismatch, taking into consideration the interactions with donor-recipient human leukocyte antigen (HLA) compatibility, and the numbers of CD34+ cells and CD3+ cells in the graft.

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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of one of the following:

    • Patients with primary refractory acute myeloid leukemia (AML), defined as ≥ 5% bone marrow blasts after two induction courses of chemotherapy
    • Primary refractory AML, defined as ≥ 5% bone marrow blasts after two induction courses of chemotherapy
    • AML or myelodysplastic syndrome with -5/5q- or monosomy 7 without inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBPα mutations
    • Relapsed AML (≥ 5% bone marrow blasts) who meet the customary WHO criteria for AML
    • AML and high FLT3 internal tandem duplication allelic ratio (high FLT3-ITD AR), defined as > 0.4
    • All cases of therapy-related AML (therapy-related AML is considered high risk)
    • Patients with AML, without inv(16)/t(16;16) or t(8;21), monosomy 7, -5/5q-, NPM, or CEPBα mutations, or high FLT3-ITD AR, but with evidence of residual AML (≥ 0.1%) at the end of Induction I; or if a minimal residual disease (MRD) is not performed, then with > 15% bone marrow blasts by morphology after one induction course of chemotherapy

      • Any flow-based MRD is eligible for AAML05P1 for patients not on AAML1031, whereas patients on AAML1031 must utilize the central lab as per the AAML1031 protocol guidelines
  • No Fanconi anemia
  • Recipients of unrelated marrow or cord blood are eligible for this study


  • Karnofsky performance status (PS) (for patients over 16 years of age) or Lansky PS (for patients 16 and under) 50-100%
  • Total bilirubin ≤ 2 mg/dL
  • SGOT (AST) or SGPT (ALT) ≤ 2.5 times upper limit of normal
  • DLCO ≥ 50% OR a normal chest x-ray and pulse oximetry in patients who are unable to undergo pulmonary function tests
  • Shortening fraction ≥ 27% by ECHO
  • Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min OR creatinine adjusted according to age
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with proven or suspected bacterial sepsis, pneumonia, or meningitis are eligible provided appropriate therapeutic measures have been initiated to control the presumed or proven infection, and systemic signs are not life-threatening
  • No evidence or presence of a fungal infection within the past 30 days


  • Prior chemotherapy, radiotherapy or any antileukemic therapy allowed provided patients meet 1 of the following criteria:

    • Received initial treatment for relapsed AML
    • Patients with primary induction failure or relapse who have already received initial therapy and who may have gone on to have additional therapy prior to receiving protocol stipulated therapy on AAML05P1
  • No treatment for fungal infection within the past 30 days
  • Concurrent radiotherapy to localized painful lesions allowed
  • No other concurrent cancer chemotherapy or immunomodulating agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00553202

  Hide Study Locations
United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, California
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Children's Hospital Central California
Madera, California, United States, 93638-8762
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123-4282
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States, 30322
United States, Indiana
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States, 40536-0093
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St. Louis, Missouri, United States, 63110
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89109-2306
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2696
Dayton Children's - Dayton
Dayton, Ohio, United States, 45404-1815
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Children's Hospital
Hershey, Pennsylvania, United States, 17033-0850
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, British Columbia
Children's and Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Stella M. Davies, MBBS, PhD Children's Hospital Medical Center, Cincinnati

Responsible Party: Children's Oncology Group Identifier: NCT00553202     History of Changes
Other Study ID Numbers: AAML05P1
COG-AAML05P1 ( Other Identifier: Children's Oncology Group )
NCI-2009-00321 ( Registry Identifier: NCI Trial Identifier )
First Posted: November 5, 2007    Key Record Dates
Results First Posted: February 24, 2017
Last Update Posted: February 24, 2017
Last Verified: July 2016

Keywords provided by Children's Oncology Group:
recurrent childhood acute myeloid leukemia
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Chromosome Aberrations
Pathologic Processes
Antilymphocyte Serum
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents