Acute Myeloid Leukemia Clinical Trial

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

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.

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Full 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.

View Eligibility Criteria

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

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 2

Estimated Enrollment:

158

Study ID:

NCT00553202

Recruitment Status:

Completed

Sponsor:

Children's Oncology Group

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There are 52 Locations for this study

See Locations Near You

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

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 2

Estimated Enrollment:

158

Study ID:

NCT00553202

Recruitment Status:

Completed

Sponsor:


Children's Oncology Group

How clear is this clinincal trial information?

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