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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


Phase 2
N/A
30 Years
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

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)

Outcome Time Frame:

Up to 5 years after SCT

Safety Issue:

No

Principal Investigator

Stella M. Davies, MBBS, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati

Authority:

United States: Federal Government

Study ID:

AAML05P1

NCT ID:

NCT00553202

Start Date:

January 2008

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute myeloid leukemia
  • childhood myelodysplastic syndromes
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Monosomy

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Penn State Children's HospitalHershey, Pennsylvania  17033-0850
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Riley's Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
Nemours Children's Clinic - PensacolaPensacola, Florida  32504