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 ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00553202
First received: November 2, 2007
Last updated: May 29, 2014
Last verified: May 2014

November 2, 2007
May 29, 2014
January 2008
September 2015   (final data collection date for primary outcome measure)
  • 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)
  • 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.
  • Disease-free survival
  • Graft-versus-host disease
  • Time to recover to the donor-specific level of expression for each natural killer cell receptor
  • .Overall survival
  • Relapse
  • Transplant-related mortality
Complete list of historical versions of study NCT00553202 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
  • 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 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.
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • 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
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

Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
158
Not Provided
September 2015   (final data collection date for primary outcome measure)

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
Both
up to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00553202
AAML05P1, COG-AAML05P1, CDR0000572744
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Stella M. Davies, MBBS, PhD Children's Hospital Medical Center, Cincinnati
Children's Oncology Group
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP