Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia
Conditions
Juvenile Myelomonocytic Leukemia
Conditions: official terms
Leukemia - Leukemia, Myelomonocytic, Acute - Leukemia, Myelomonocytic, Chronic - Leukemia, Myelomonocytic, Juvenile
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: busulfan Type: Drug
Name: cyclophosphamide Type: Drug
Name: melphalan Type: Drug
Name: fludarabine phosphate Type: Drug
Name: allogeneic hematopoietic stem cell transplantation Type: Procedure
Name: tacrolimus Type: Drug
Name: mycophenolate mofetil Type: Drug
Name: pharmacological study Type: Other
Name: laboratory biomarker analysis Type: Other
Overall Status
Recruiting
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.
Detailed Description
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 18 Years
Minimum Age: 3 Months
Gender: Both
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
Locations
Children's Hospital of Alabama
Birmingham, Alabama, United States
Status: Recruiting
Contact: Alyssa T. Reddy - 205-934-0309
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Status: Recruiting
Contact: Jessica Boklan - 602-546-0920
City of Hope
Duarte, California, United States
Status: Recruiting
Contact: Anna B. Pawlowska - 800-826-4673 - becomingapatient@coh.org
Mattel Children's Hospital UCLA
Los Angeles, California, United States
Status: Recruiting
Contact: Theodore B. Moore - 310-825-6708
Rady Children's Hospital - San Diego
San Diego, California, United States
Status: Recruiting
Contact: William D. Roberts - 858-966-5934
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States
Status: Recruiting
Contact: Christopher C. Dvorak - 877-827-3222
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Status: Recruiting
Contact: Christopher N. Frantz - 302-651-5755
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States
Status: Recruiting
Contact: Scott M. Bradfield - 904-697-3529
All Children's Hospital
Saint Petersburg, Florida, United States
Status: Recruiting
Contact: Gregory A. Hale - 727-767-2423 - HamblinF@allkids.org
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Status: Recruiting
Contact: Ann E. Haight - 888-785-1112
Riley Hospital for Children
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Robert J. Fallon - 317-274-2552
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Status: Recruiting
Contact: Ayman A. El-Sheikh - 800-237-1225
Kosair Children's Hospital
Louisville, Kentucky, United States
Status: Recruiting
Contact: Alexandra C. Cheerva - 866-530-5516
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Status: Recruiting
Contact: Allen R. Chen - 410-955-8804 - jhcccro@jhmi.edu
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
Contact: Leslie E. Lehmann - 866-790-4500
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Status: Recruiting
Contact: Sureyya Savasan - 313-576-9363
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States
Status: Recruiting
Contact: Michael R. Verneris - 612-624-2620
The Childrens Mercy Hospital
Kansas City, Missouri, United States
Status: Recruiting
Contact: Maxine L. Hetherington - 816-234-3265
Hackensack University Medical Center
Hackensack, New Jersey, United States
Status: Recruiting
Contact: Jennifer A. Krajewski - 201-996-2879
Montefiore Medical Center - Moses Campus
Bronx, New York, United States
Status: Recruiting
Contact: Peter D. Cole - 718-904-2730 - aecc@aecom.yu.edu
Columbia University Medical Center
New York, New York, United States
Status: Recruiting
Contact: Alice Lee - 212-305-8615
New York Medical College
Valhalla, New York, United States
Status: Recruiting
Contact: Mehmet F. Ozkaynak - 914-594-3794
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Status: Recruiting
Contact: John P. Perentesis - 513-636-2799
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Status: Recruiting
Contact: Yousif (Joe) H. Matloub - 216-844-5437
Nationwide Children's Hospital
Columbus, Ohio, United States
Status: Recruiting
Contact: Mark A. Ranalli - 614-722-2708
Oregon Health and Science University
Portland, Oregon, United States
Status: Recruiting
Contact: Eneida R. Nemecek - 503-494-1080 - trials@ohsu.edu
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Status: Active, not recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Status: Recruiting
Contact: Randy M. Windreich - 412-692-5573
Medical University of South Carolina
Charleston, South Carolina, United States
Status: Recruiting
Contact: Jacqueline M. Kraveka - 843-792-9321
Medical City Dallas Hospital
Dallas, Texas, United States
Status: Recruiting
Contact: Carl Lenarsky - 972-566-5588
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Status: Recruiting
Contact: Victor M. Aquino - 214-648-7097
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Status: Recruiting
Contact: Jaime Estrada - 210-575-7000
Primary Children's Hospital
Salt Lake City, Utah, United States
Status: Recruiting
Contact: Phillip E. Barnette - 801-585-5270
Seattle Children's Hospital
Seattle, Washington, United States
Status: Recruiting
Contact: Douglas S. Hawkins - 866-987-2000
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Status: Recruiting
Contact: Kenneth B. DeSantes - 608-262-5223
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Status: Recruiting
Contact: Catherine H. Cole - (08) 9340 8330 - admin@childcancerresearch.com.au
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Status: Recruiting
Contact: Rochelle A. Yanofsky - 866-561-1026 - CIO_Web@cancercare.mb.ca
Starship Children's Hospital
Grafton, Auckland, New Zealand
Status: Recruiting
Contact: Lochie R. Teague - 0800 728 436
Start Date
June 2013
Sponsors
Children's Oncology Group
Source
Children's Oncology Group
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page