In English | En español
Questions About Cancer? 1-800-4-CANCER

Clinical Trials (PDQ®)

Page Options

  • Print This Page
  • Email This Document
Clinical Trial Questions?
Get Help:
1-800-4-CANCER
LiveHelp online chat

Clinical Trials (PDQ®)

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
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive3 to 18NCI, OtherASCT1221
NCI-2013-00738, COG-ASCT1221, U10CA180886, U10CA098543, NCT01824693

Trial Description

Summary

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

PRIMARY OBJECTIVES:

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.

Eligibility Criteria

Inclusion Criteria:

  • 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:
  • 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 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

Christopher Dvorak, MDPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 Children's Hospital of Alabama at University of Alabama at Birmingham
 Alyssa T Reddy Ph: 205-934-0309
Arizona
  Phoenix
 Phoenix Children's Hospital
 Jessica Boklan Ph: 602-546-0920
California
  Duarte
 City of Hope Comprehensive Cancer Center
 Anna B Pawlowska Ph: 800-826-4673
  Email: becomingapatient@coh.org
  Los Angeles
 Mattel Children's Hospital at UCLA
 Theodore B Moore Ph: 310-825-6708
  Orange
 Children's Hospital of Orange County
 Violet Shen Ph: 714-997-3000
  San Diego
 Rady Children's Hospital - San Diego
 William D Roberts Ph: 858-966-5934
  San Francisco
 UCSF Helen Diller Family Comprehensive Cancer Center
 Christopher C Dvorak Ph: 877-827-3222
Florida
  Saint Petersburg
 All Children's Hospital
 Gregory A Hale Ph: 727-767-2423
  Email: HamblinF@allkids.org
Georgia
  Atlanta
 AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
 Ann E Haight Ph: 888-785-1112
Illinois
  Chicago
 Ann and Robert H. Lurie Children's Hospital of Chicago
 Sonali Chaudhury Ph: 773-880-4562
Indiana
  Indianapolis
 Riley's Children Cancer Center at Riley Hospital for Children
 Robert J Fallon Ph: 317-274-2552
Iowa
  Iowa City
 Holden Comprehensive Cancer Center at University of Iowa
 Ayman A El-Sheikh Ph: 800-237-1225
Kentucky
  Louisville
 Kosair Children's Hospital
 Alexandra C Cheerva Ph: 866-530-5516
Maryland
  Baltimore
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Allen R. Chen Ph: 410-955-8804
  Email: jhcccro@jhmi.edu
Michigan
  Detroit
 Wayne State University
 Sureyya Savasan Ph: 313-576-9363
Minnesota
  Minneapolis
 Masonic Cancer Center at University of Minnesota
 Michael R Verneris Ph: 612-624-2620
Mississippi
  Jackson
 University of Mississippi Cancer Clinic
 Gail C Megason Ph: 601-815-6700
Missouri
  Kansas City
 Children's Mercy Hospital
 Maxine L Hetherington Ph: 816-234-3265
Nebraska
  Omaha
 Fred and Pamela Buffett Cancer Center
 Minnie Abromowitch Ph: 402-955-3949
New Jersey
  Hackensack
 Hackensack University Medical Center Cancer Center
 Jennifer A Krajewski Ph: 201-996-2879
New York
  Bronx
 Montefiore Medical Center
 Peter D Cole Ph: 718-904-2730
  Email: aecc@aecom.yu.edu
  New York
 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
 Alice Lee Ph: 212-305-8615
  Rochester
 James P. Wilmot Cancer Center at University of Rochester Medical Center
 Jeffrey R Andolina Ph: 585-275-5830
  Valhalla
 New York Medical College
 Mehmet F Ozkaynak Ph: 914-594-3794
Ohio
  Cincinnati
 Cincinnati Children's Hospital Medical Center
 John P Perentesis Ph: 513-636-2799
  Cleveland
 Seidman Cancer Center at University Hospitals/Case Medical Center
 Yousif (Joe) H Matloub Ph: 216-844-5437
  Columbus
 Nationwide Children's Hospital
 Mark A Ranalli Ph: 614-722-2708
Oklahoma
  Oklahoma City
 Oklahoma University Cancer Institute
 Rene Y McNall-Knapp Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Oregon
  Portland
 Knight Cancer Institute at Oregon Health and Science University
 Eneida R Nemecek Ph: 503-494-1080
  Email: trials@ohsu.edu
Pennsylvania
  Philadelphia
 Children's Hospital of Philadelphia
 Stephan A Grupp Ph: 215-590-2810
  Pittsburgh
 Children's Hospital of Pittsburgh of UPMC
 Randy M Windreich Ph: 412-692-5573
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Jacqueline M Kraveka Ph: 843-792-9321
Texas
  Dallas
 Medical City Dallas Hospital
 Carl Lenarsky Ph: 972-566-5588
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 Victor M Aquino Ph: 214-648-7097
  Fort Worth
 Cook Children's Medical Center - Fort Worth
 Mary Meaghan P Granger Ph: 682-885-2103
  San Antonio
 Methodist Children's Hospital of South Texas
 Jaime Estrada Ph: 210-575-7000
Utah
  Salt Lake City
 Primary Children's Medical Center
 Phillip E Barnette Ph: 801-585-5270
Washington
  Seattle
 Children's Hospital and Regional Medical Center - Seattle
 Douglas S Hawkins Ph: 866-987-2000
Wisconsin
  Madison
 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
 Kenneth B DeSantes Ph: 608-262-5223
Australia
Western Australia
  Perth
 Princess Margaret Hospital for Children
 Catherine H Cole Ph: (08) 9340 8330
  Email: admin@childcancerresearch.com.au
Canada
British Columbia
  Vancouver
 Children's and Women's Hospital of British Columbia
 Caron Strahlendorf Ph: 604-875-2345ext6477
Manitoba
  Winnipeg
 CancerCare Manitoba
 Rochelle A Yanofsky Ph: 866-561-1026
  Email: CIO_Web@cancercare.mb.ca
Quebec
  Montreal
 Montreal Children's Hospital at McGill University Health Center
 Sharon B Abish Ph: 514-412-4445
  Email: info@thechildren.com
New Zealand
Auckland
  Grafton
 Starship Children's Health
 Lochie R Teague Ph:  0800 728 436

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01824693
ClinicalTrials.gov processed this data on November 12, 2014

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.

Back to TopBack to Top