DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

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

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: anti-thymocyte globulin (Biological); busulfan (Drug); cyclophosphamide (Drug); cyclosporine (Drug); methotrexate (Drug); methylprednisolone (Drug); tacrolimus (Drug); laboratory biomarker analysis (Other); pharmacological study (Other); allogeneic bone marrow transplantation (Procedure); allogeneic hematopoietic stem cell transplantation (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Stella M. Davies, MBBS, PhD, Study Chair, Affiliation: Children's Hospital Medical Center, Cincinnati


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.

Clinical Details

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

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

Primary outcome:

Overall survival

Time to NK cell reconstitution

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


- 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.


Minimum age: N/A. Maximum age: 30 Years. Gender(s): Both.



- 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

Locations and Contacts

UAB Comprehensive Cancer Center, Birmingham, Alabama 35294, United States

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States

Children's and Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States

Children's Hospital Central California, Madera, California 93638-8762, United States

Rady Children's Hospital - San Diego, San Diego, California 92123-4282, United States

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States

Nemours Children's Clinic, Jacksonville, Florida 32207, United States

Nemours Children's Clinic - Orlando, Orlando, Florida 32806, United States

Nemours Children's Clinic - Pensacola, Pensacola, Florida 32504, United States

All Children's Hospital, Saint Petersburg, Florida 33701, United States

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus, Atlanta, Georgia 30322, United States

Riley's Children Cancer Center at Riley Hospital for Children, Indianapolis, Indiana 46202, United States

Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242-1002, United States

Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States

Kosair Children's Hospital, Louisville, Kentucky 40232, United States

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States

Children's Mercy Hospital, Kansas City, Missouri 64108, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States

CCOP - Nevada Cancer Research Foundation, Las Vegas, Nevada 89109-2306, United States

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States

Nationwide Children's Hospital, Columbus, Ohio 43205-2696, United States

Dayton Children's - Dayton, Dayton, Ohio 45404-1815, United States

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States

McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Penn State Children's Hospital, Hershey, Pennsylvania 17033-0850, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15213, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

East Tennessee Children's Hospital, Knoxville, Tennessee 37916, United States

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States

CCOP - Scott and White Hospital, Temple, Texas 76508, United States

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States

Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Midwest Children's Cancer Center at Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2008
Last updated: June 1, 2015

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017