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

NCT ID: NCT00553202

Last Updated: 2020-04-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2020-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

busulfan

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

cyclosporine

Intervention Type DRUG

Given IV or orally

methotrexate

Intervention Type DRUG

Given IV

methylprednisolone

Intervention Type DRUG

Given IV

tacrolimus

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

allogeneic bone marrow transplantation

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo allogeneic hematopoietic SCT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

anti-thymocyte globulin

Given IV

Intervention Type BIOLOGICAL

busulfan

Given IV

Intervention Type DRUG

cyclophosphamide

Given IV

Intervention Type DRUG

cyclosporine

Given IV or orally

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

methylprednisolone

Given IV

Intervention Type DRUG

tacrolimus

Given IV

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

pharmacological study

Correlative studies

Intervention Type OTHER

allogeneic bone marrow transplantation

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

allogeneic hematopoietic stem cell transplantation

Undergo allogeneic hematopoietic SCT

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Rabbit ATG RATG-Rabbit Antithymocyte Globulin Thymoglobulin NSC #720095 Busulfex NSC #750 Cytoxan NSC #26271 CYA Sandimmune Neoral Gengraf NSC #290193 MTX amethopterin NSC #000740 Solu-Medrol A-Methapred Medrol NSC #19987 FK-506 Prograf NSC #717865 bone marrow therapy allogeneic allogenic transplantation allogeneic bone marrow allogenic bone marrow

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Stella M. Davies, MBBS, PhD

Role: STUDY_CHAIR

Children's Hospital Medical Center, Cincinnati

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

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

Long Beach, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

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

Atlanta, Georgia, United States

Site Status

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

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

Rochester, New York, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's - Dayton

Dayton, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

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

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

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

Milwaukee, Wisconsin, United States

Site Status

Children's and Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

COG-AAML05P1

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00321

Identifier Type: REGISTRY

Identifier Source: secondary_id

AAML05P1

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Post-transplant Flotetuzumab for AML
NCT05506956 COMPLETED PHASE1