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
Leukemia
About this trial
This is an interventional treatment trial for Leukemia focused on measuring recurrent childhood acute myeloid leukemia, childhood myelodysplastic syndromes
Eligibility 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
Sites / Locations
- UAB Comprehensive Cancer Center
- Phoenix Children's Hospital
- Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
- Children's Hospital Central California
- Rady Children's Hospital - San Diego
- Alfred I. duPont Hospital for Children
- Children's National Medical Center
- Lee Cancer Care of Lee Memorial Health System
- Nemours Children's Clinic
- Nemours Children's Clinic - Orlando
- Nemours Children's Clinic - Pensacola
- All Children's Hospital
- AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
- Riley's Children Cancer Center at Riley Hospital for Children
- Holden Comprehensive Cancer Center at University of Iowa
- Lucille P. Markey Cancer Center at University of Kentucky
- Kosair Children's Hospital
- Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
- Barbara Ann Karmanos Cancer Institute
- Mayo Clinic Cancer Center
- University of Mississippi Cancer Clinic
- Children's Mercy Hospital
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- UNMC Eppley Cancer Center at the University of Nebraska Medical Center
- CCOP - Nevada Cancer Research Foundation
- Hackensack University Medical Center Cancer Center
- Roswell Park Cancer Institute
- Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
- James P. Wilmot Cancer Center at University of Rochester Medical Center
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
- Blumenthal Cancer Center at Carolinas Medical Center
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Children's Hospital
- Nationwide Children's Hospital
- Dayton Children's - Dayton
- Oklahoma University Cancer Institute
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- East Tennessee Children's Hospital
- St. Jude Children's Research Hospital
- Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
- Cook Children's Medical Center - Fort Worth
- Methodist Children's Hospital of South Texas
- CCOP - Scott and White Hospital
- Primary Children's Medical Center
- Virginia Commonwealth University Massey Cancer Center
- Midwest Children's Cancer Center at Children's Hospital of Wisconsin
- Children's and Women's Hospital of British Columbia
- McMaster Children's Hospital at Hamilton Health Sciences
- Hospital for Sick Children
- Hopital Sainte Justine
Arms of the Study
Arm 1
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