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LeukemiaPhase 2NCT00553202

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

A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclophosphamide in people with Leukemia, run by Children's Oncology Group at 52 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Leukemia
What is being tested?
anti-thymocyte globulin, busulfan and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
52 sitesin 2 countries
Study dates
Jan 2008to 31 Mar 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

52 sites in 2 countries.

52 sites in 2 countries

United States48 sites

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

    Atlanta, Georgia, 30322

  • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Baltimore, Maryland, 21215

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Dayton Children's - Dayton

    Dayton, Ohio, 45404-1815

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033-0850

  • Riley's Children Cancer Center at Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37916

  • CCOP - Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89109-2306

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

    Long Beach, California, 90801

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Children's Hospital Central California

    Madera, California, 93638-8762

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-6805

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15213

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123-4282

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada4 sites

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's and Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

About this study

Official title: 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.

Read the detailed 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.

Conditions
Leukemia
Being tested
anti-thymocyte globulin, busulfan, cyclophosphamide, cyclosporine, methotrexate
Keywords
recurrent childhood acute myeloid leukemia, childhood myelodysplastic syndromes
Medical subject headings
Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • anti-thymocyte globulinBiological

    Also called Rabbit ATG, RATG-Rabbit, Antithymocyte Globulin, Thymoglobulin

    Given IV

  • busulfanDrug

    Also called Busulfex, NSC #750

    Given IV

  • cyclophosphamideDrug

    Also called Cytoxan, NSC #26271

    Given IV

  • cyclosporineDrug

    Also called CYA, Sandimmune, Neoral, Gengraf

    Given IV or orally

  • methotrexateDrug

    Also called MTX, amethopterin, NSC #000740

    Given IV

  • methylprednisoloneDrug

    Also called Solu-Medrol, A-Methapred, Medrol, NSC #19987

    Given IV

  • tacrolimusDrug

    Also called FK-506, Prograf, NSC #717865

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Correlative studies

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, allogenic, transplantation

    allogeneic bone marrow transplantation

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic hematopoietic SCT

Study groups in NCT00553202
Study groupRoleWhat they receive
Treatment (chemotherapy and allogeneic SCT)ExperimentalPatients 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
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    OS - Time from HSCT until death

    Measured: At 5 years from HSCT date

  2. Cumulative Incidence of NK Cell Reconstitution

    Cumulative incidence of successful reconstitution to donor level is calculated.

    Measured: At 5 years from HSCT date

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2007 (estimated)
  2. Study startJan 2008
  3. Primary completionJun 2016
  4. Study completion31 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
158 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00553202
Sponsor's protocol ID
AAML05P1
Other IDs
COG-AAML05P1, NCI-2009-00321
Status last verified
Jul 2016
First submitted
2 Nov 2007
Last updated
16 Apr 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclophosphamide in people with Leukemia, run by Children's Oncology Group at 52 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: At 5 years from HSCT date). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00553202.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2020.

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