Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Active||3 to 18||NCI, Other||ASCT1221|
NCI-2013-00738, COG-ASCT1221, U10CA180886, U10CA098543, NCT01824693
This randomized phase II trial studies how well giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before donor hematopoietic cell transplant works in treating younger patients with juvenile myelomonocytic leukemia. Giving chemotherapy before a donor hematopoietic transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before a donor stem cell transplant is more effective in treating juvenile myelomonocytic leukemia.
Further Study Information
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.
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.
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.
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).
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.
- Patients must have a strong clinical suspicion of JMML, based on a modified category 1 of the revised diagnostic criteria; specifically, eligible patients must have all of the following:
- 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
- Patients with a known germline mutation of PTPN11 (Noonan's Syndrome) are not eligible
- 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
Trial Contact Information
Trial Lead Organizations/Sponsors
Children's Oncology Group
- National Cancer Institute
Children's Hospital of Alabama at University of Alabama at Birmingham
Alyssa T Reddy
Phoenix Children's Hospital
City of Hope Comprehensive Cancer Center
Anna B Pawlowska
Mattel Children's Hospital at UCLA
Theodore B Moore
Children's Hospital of Orange County
UCSF Helen Diller Family Comprehensive Cancer Center
Christopher C Dvorak
Alfred I. duPont Hospital for Children
Scott M Bradfield
Nemours Children's Clinic
Scott M Bradfield
All Children's Hospital
Gregory A Hale
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Ann E Haight
Ann and Robert H. Lurie Children's Hospital of Chicago
Riley's Children Cancer Center at Riley Hospital for Children
Robert J Fallon
Holden Comprehensive Cancer Center at University of Iowa
Ayman A El-Sheikh
Kosair Children's Hospital
Alexandra C Cheerva
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Allen R. Chen
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Leslie E Lehmann
Wayne State University
Masonic Cancer Center at University of Minnesota
Michael R Verneris
University of Mississippi Cancer Clinic
Gail C Megason
Children's Mercy Hospital
Maxine L Hetherington
Cardinal Glennon Children's Hospital
William S Ferguson
Fred and Pamela Buffett Cancer Center
Hackensack University Medical Center Cancer Center
Jennifer A Krajewski
Montefiore Medical Center
Peter D Cole
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
James P. Wilmot Cancer Center at University of Rochester Medical Center
Jeffrey R Andolina
New York Medical College
Jessica C Hochberg
Cincinnati Children's Hospital Medical Center
John P Perentesis
Seidman Cancer Center at University Hospitals/Case Medical Center
Yousif (Joe) H Matloub
Nationwide Children's Hospital
Mark A Ranalli
Stephenson Cancer Center at the University of Oklahoma
Rene Y McNall-Knapp
Knight Cancer Institute at Oregon Health and Science University
Eneida R Nemecek
Children's Hospital of Philadelphia
Stephan A Grupp
Children's Hospital of Pittsburgh of UPMC
Randy M Windreich
Hollings Cancer Center at Medical University of South Carolina
Jacqueline M Kraveka
Medical City Dallas Hospital
Stanton C Goldman
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Victor M Aquino
Cook Children's Medical Center - Fort Worth
Mary Meaghan P Granger
Methodist Children's Hospital of South Texas
Salt Lake City
Primary Children's Medical Center
Phillip E Barnette
Children's Hospital and Regional Medical Center - Seattle
Douglas S Hawkins
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Kenneth B DeSantes
Princess Margaret Hospital for Children
Catherine H Cole
Ph: (08) 9340 8222
Children's and Women's Hospital of British Columbia
Rochelle A Yanofsky
Hopital Sainte Justine
Montreal Children's Hospital at McGill University Health Center
Sharon B Abish
Starship Children's Health
Lochie R Teague
Ph: 0800 728 436
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01824693
ClinicalTrials.gov processed this data on April 09, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.