Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia
NCT ID: NCT01824693
Last Updated: 2018-12-05
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
30 participants
INTERVENTIONAL
2013-06-24
2017-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome
NCT00445744
Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00301834
Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Advanced Hematologic Cancer
NCT00014469
Stem Cell Transplant in Treating Patients With Hematological Cancer or Other Disorders
NCT00740467
Busulfan and Cyclophosphamide Followed by Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT00004896
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To compare ? in a randomized fashion ? the day 100 treatment related mortality (TRM) incidence for two myeloablative conditioning regimens, busulfan-fludarabine (fludarabine phosphate) (BU-FLU) and busulfan-cyclophosphamide-melphalan (BU-CY-MEL), prior to hematopoietic cell transplant (HCT) for children with juvenile myelomonocytic leukemia (JMML), in order to determine the preferred regimen for future trials.
II. To compare ? in a randomized fashion ? the 18-month event-free survival (EFS) following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML, in order to determine the preferred regimen for future trials.
SECONDARY OBJECTIVES:
I. To determine the 18-month relapse incidence (RI) following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML.
II. To determine the graft failure rates following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML.
TERTIARY OBJECTIVES:
I. To determine the rates of severe toxicities (grade 3/4) at day 100 post-HCT between the two myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL).
II. To determine the rates of acute and chronic (at 18 months post-HCT) graft-versus-host disease (GVHD) following HCT using two different conditioning regimens (BU-FLU vs. BU-CY-MEL) in children with JMML.
III. To create a JMML-specific pre-HCT index to allow better risk-stratification of future patients.
IV. To determine the feasibility of assessing post-transplant disease burden by donor chimerism measurements and allele-specific polymerase chain reaction (PCR) in mononuclear and sorted cell subsets.
V. To validate gene expression and methylation classifiers predictive of relapse in patients with JMML.
VI. To comprehensively assess genetic and biochemical alterations amongst patients with JMML who are treated on this transplant protocol.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I:
CONDITIONING REGIMEN: Patients receive busulfan intravenously (IV) over 2-3 hours once daily (QD), every 12 hours, or every 6 hours on days -8 to -5, cyclophosphamide IV over 60 minutes QD on days -4 and -3, and melphalan IV over 15-30 minutes on day -1.
TRANSPLANT: Patients undergo allogeneic HCT on day 0.
Patients receive tacrolimus IV or orally (PO) on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).
ARM II:
CONDITIONING REGIMEN: Patients receive busulfan as in Arm I and fludarabine phosphate IV over 30-60 minutes on days -5 to -2.
TRANSPLANT: Patients undergo allogeneic HCT as in Arm I.
Patients receive tacrolimus IV or PO on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).
After completion of study treatment, patients are followed up for 5 years.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm I (busulfan, cyclophosphamide, melphalan)
CONDITIONING REGIMEN: Patients receive busulfan IV QD, every 12 hours, or every 6 hours over 2-3 hours on days -8 to -5, cyclophosphamide IV QD over 60 minutes on days -4 and -3, and melphalan IV over 15-30 minutes on day -1.
TRANSPLANT: Patients undergo allogeneic HCT no sooner than 24 hours after the last dose of chemotherapy.
Patients receive tacrolimus IV or PO on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HCT
Busulfan
Given IV
Cyclophosphamide
Given IV
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Mycophenolate Mofetil
Given IV or PO
Pharmacological Study
Correlative studies
Tacrolimus
Given IV or PO
Arm II (busulfan, fludarabine phosphate)
CONDITIONING REGIMEN: Patients receive busulfan as in Arm I and fludarabine phosphate IV over 1 hour on days -5 to -2.
TRANSPLANT: Patients undergo allogeneic HCT as in Arm I.
Patients receive tacrolimus IV or PO on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HCT
Busulfan
Given IV
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given IV or PO
Pharmacological Study
Correlative studies
Tacrolimus
Given IV or PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HCT
Busulfan
Given IV
Cyclophosphamide
Given IV
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Mycophenolate Mofetil
Given IV or PO
Pharmacological Study
Correlative studies
Tacrolimus
Given IV or PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Splenomegaly
* Absolute monocyte count (AMC) \> 1000/uL
* Blasts in peripheral blood (PB)/bone marrow (BM) \< 20%
* For the 7-10% of patients without splenomegaly, the diagnostic entry criteria must include all other features described above and at least 2 of the following criteria:
* Circulating myeloid precursors
* White blood cell (WBC) \> 10,000/uL
* Increased fetal hemoglobin (HgbF) for age
* Sargramostim (GM-CSF) hypersensitivity OR, patients must have been previously diagnosed with JMML
* Patients must be previously untreated with HCT
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria
* Patients with a known history of NF1 (Neurofibromatosis Type 1) and either
* A history of a tumor of the central nervous system (astrocytoma or optic glioma), or
* A malignant peripheral nerve sheath tumor with a complete remission of \< 1 year are not eligible
* Human immunodeficiency virus (HIV) positive patients are not eligible
3 Months
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Christopher Dvorak
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Mattel Children's Hospital UCLA
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Childrens Mercy Hospital
Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
New York Medical College
Valhalla, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Medical City Dallas Hospital
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Starship Children's Hospital
Grafton, Auckland, New Zealand
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2013-00738
Identifier Type: REGISTRY
Identifier Source: secondary_id
COG-ASCT1221
Identifier Type: -
Identifier Source: secondary_id
ASCT1221
Identifier Type: -
Identifier Source: secondary_id
ASCT1221
Identifier Type: OTHER
Identifier Source: secondary_id
ASCT1221
Identifier Type: OTHER
Identifier Source: secondary_id
ASCT1221
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.