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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
30 Years
Open (Enrolling)

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


- 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

- 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


- 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 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

Type of Study:


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:


Principal Investigator

Stella M. Davies, MBBS, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Federal Government

Study ID:




Start Date:

January 2008

Completion Date:

Related Keywords:

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



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