Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia

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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, MD, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

Children's Hospital of Alabama at University of Alabama at Birmingham

Alyssa T Reddy
Ph: 888-823-5923
Email: ctsucontact@westat.com

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 Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

Christopher C Dvorak
Ph: 877-827-3222

Delaware
Wilmington

Alfred I. duPont Hospital for Children

Scott M Bradfield
Ph: 904-697-3529

Florida
Jacksonville

Nemours Children's Clinic

Scott M Bradfield
Ph: 904-697-3529

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: 888-823-5923
Email: ctsucontact@westat.com

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

Massachusetts
Boston

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Leslie E Lehmann
Ph: 866-790-4500

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

Saint Louis

Cardinal Glennon Children's Hospital

William S Ferguson
Ph: 314-268-4000

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

Jessica C Hochberg
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

Stephenson Cancer Center at the University of Oklahoma

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

Stanton C Goldman
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 8222
Email: catherine.cole@health.wa.gov.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

Hopital Sainte Justine

Yvan Samson
Ph: 514-345-4931

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 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.