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

This study is currently recruiting participants.
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00553202
First received: November 2, 2007
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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: This phase II trial is studying donor stem cell transplant to see how well it works in treating young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed acute myelogenous leukemia.


Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years after SCT ] [ Designated as safety issue: No ]
    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)

  • 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 ] [ Designated as safety issue: No ]
    The cumulative incidence of relapse or death after SCT will be calculated by considering relapse and death due to other causes as competing events.

  • Acute and chronic graft-versus-host disease [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Acute and chronic GVHD will be summarized.

  • Time to NK cell reconstitution [ Time Frame: At baseline (donor pre-SCT) and up to 12 months post-SCT (recipient) ] [ Designated as safety issue: No ]
    Cumulative incidence of successful reconstitution to donor level will be calculated.

  • Time to the donor-specific NK-cell receptor expression [ Time Frame: Up to 42 days after SCT ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 400
Study Start Date: January 2008
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Cyclosporine
  • 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

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00553202

  Hide Study Locations
Locations
United States, Alabama
UAB Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - UAB Comprehensive Cancer Center    205-934-0309      
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016-7710
Contact: Jessica Boklan    602-546-0920      
United States, California
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital Recruiting
Long Beach, California, United States, 90801
Contact: Amanda M. Termuhlen    562-933-8605      
Children's Hospital Central California Recruiting
Madera, California, United States, 93638-8762
Contact: Vonda L. Crouse    559-353-5480      
Rady Children's Hospital - San Diego Recruiting
San Diego, California, United States, 92123-4282
Contact: Clinical Trials Office - Rady Children's Hospital - San Diego    858-966-5934      
United States, Delaware
Alfred I. duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Clinical Trials Office - Alfred I. duPont Hospital for Childre    302-651-5755      
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Clinical Trials Office - Children's National Medical Center    202-884-2549      
United States, Florida
Lee Cancer Care of Lee Memorial Health System Recruiting
Fort Myers, Florida, United States, 33901
Contact: Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt    877-680-0008      
Nemours Children's Clinic Recruiting
Jacksonville, Florida, United States, 32207
Contact: Eric S. Sandler    904-697-3793      
Nemours Children's Clinic - Orlando Recruiting
Orlando, Florida, United States, 32806
Contact: Ramamoorthy Nagasubramanian    407-650-7230      
Nemours Children's Clinic - Pensacola Recruiting
Pensacola, Florida, United States, 32504
Contact: Jeffrey H. Schwartz    850-505-4790      
All Children's Hospital Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Gregory A. Hale    727-767-4176      
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Recruiting
Atlanta, Georgia, United States, 30322
Contact: Todd M. Cooper    404-785-1838      
United States, Indiana
Riley's Children Cancer Center at Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: James M. Croop    317-944-8784      
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa Recruiting
Iowa City, Iowa, United States, 52242-1002
Contact: Cancer Information Service    800-237-1225      
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536-0093
Contact: Clinical Trials Office - Markey Cancer Center at University of    859-257-3379      
Kosair Children's Hospital Recruiting
Louisville, Kentucky, United States, 40232
Contact: Clinical Trials Office - Kosair Children's Hospital    502-629-5500    CancerResource@nortonhealthcare.org   
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Recruiting
Baltimore, Maryland, United States, 21215
Contact: Joseph M. Wiley    410-601-6266      
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute    313-576-9363      
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
United States, Mississippi
University of Mississippi Cancer Clinic Recruiting
Jackson, Mississippi, United States, 39216-4505
Contact: Gail C. Megason    601-984-5220      
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Maxine L. Hetherington    816-234-3265      
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Recruiting
St. Louis, Missouri, United States, 63110
Contact: Robert J. Hayashi    314-454-2041      
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Clinical Trials Office - UNMC Eppley Cancer Center at the Univ    800-999-5465      
United States, Nevada
CCOP - Nevada Cancer Research Foundation Recruiting
Las Vegas, Nevada, United States, 89109-2306
Contact: Jonathan Bernstein    702-732-1493      
United States, New Jersey
Hackensack University Medical Center Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Clinical Trials Office - Hackensack University Medical Center    201-996-2879      
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263-0001
Contact: Clinical Trials Office - Roswell Park Cancer Institute    877-275-7724      
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C    212-305-8615      
James P. Wilmot Cancer Center at University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Jeffrey R. Andolina    585-275-2981      
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office - Lineberger Comprehensive Cancer Cente    877-668-0683      
Contact    919-966-4432      
Blumenthal Cancer Center at Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28232-2861
Contact: Clinical Trials Office - Blumenthal Cancer Center at Carolinas    704-355-2884      
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica    513-636-2799      
Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106-5000
Contact: Yousif (Joe) H. Matloub    216-844-3345      
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205-2696
Contact: Laura T. Martin    614-722-3582      
Dayton Children's - Dayton Recruiting
Dayton, Ohio, United States, 45404-1815
Contact: Emmett H. Broxson    937-641-3111      
United States, Oklahoma
Oklahoma University Cancer Institute Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Rene Y. McNall-Knapp    405-271-5311      
United States, Pennsylvania
Penn State Children's Hospital Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Lisa M. McGregor    717-531-6012      
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Elizabeth Fox    267-425-3010      
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Clinical Trials Office - Children's Hospital of Pittsburgh    412-692-7056      
United States, Tennessee
East Tennessee Children's Hospital Recruiting
Knoxville, Tennessee, United States, 37916
Contact: Ray C. Pais    865-541-8266      
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Clinical Trials Office - St. Jude Children's Research Hospital    901-595-4644      
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Clinical Trials Office - Simmons Comprehensive Cancer Center a    866-460-4673      
Contact    214-648-7097      
Cook Children's Medical Center - Fort Worth Recruiting
Fort Worth, Texas, United States, 76104
Contact: Clinical Trials Office - Cook's Children's Medical Center    682-885-2103      
Methodist Children's Hospital of South Texas Recruiting
San Antonio, Texas, United States, 78229-3993
Contact: Jaime Estrada    210-575-7268      
CCOP - Scott and White Hospital Recruiting
Temple, Texas, United States, 76508
Contact: Guy H. Grayson    254-724-2006      
United States, Utah
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84113-1100
Contact: Phillip E. Barnette    801-662-4700      
United States, Virginia
Virginia Commonwealth University Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23298-0037
Contact: Clinical Trials Office -Virginia Commonwealth University Masse    804-628-1939      
United States, Wisconsin
Midwest Children's Cancer Center at Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Michael E. Kelly    414-456-4170      
Canada, British Columbia
Children's and Women's Hospital of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Caron Strahlendorf    604-875-3576      
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Carol Portwine    905-521-2100x73464      
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Sylvain Baruchel    416-813-7795      
Canada, Quebec
Hopital Sainte Justine Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Yvan Samson    514-345-4931x2790      
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Stella M. Davies, MBBS, PhD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00553202     History of Changes
Other Study ID Numbers: AAML05P1, COG-AAML05P1, CDR0000572744
Study First Received: November 2, 2007
Last Updated: February 11, 2014
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Monosomy
Neoplasms by Histologic Type
Neoplasms
Aneuploidy
Chromosome Aberrations
Pathologic Processes
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Tacrolimus
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014