NCT00412360

Brief Summary

This study is a Phase III, randomized, open-label, multi-center, prospective study of single umbilical cord blood (UCB) transplantation versus double UCB transplantation in pediatric patients with hematologic malignancies.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
224

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Dec 2006

Longer than P75 for phase_3

Geographic Reach
3 countries

38 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2006

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

December 14, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 18, 2006

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2014

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 21, 2015

Completed
Last Updated

October 28, 2021

Status Verified

October 1, 2021

Enrollment Period

7.3 years

First QC Date

December 14, 2006

Results QC Date

August 28, 2015

Last Update Submit

October 13, 2021

Conditions

Keywords

Double cord blood

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Overall Survival

    Overall survival is defined as survival of death from any cause.

    1 year post-randomization

Secondary Outcomes (9)

  • Percentage of Participants With Disease-free Survival

    1 year post-randomization

  • Percentage of Participants With Neutrophil and Platelet Engraftment

    Days 42 and 100

  • Time to Neutrophil and Platelet Engraftment

    2 years post-transplant

  • Percentage of Participants With Acute Graft-versus-host Disease (GVHD)

    Day 100 post-randomization

  • Percentage of Participants With Chronic GVHD

    1 year post-randomization

  • +4 more secondary outcomes

Study Arms (2)

Single Cord Blood Transplant

EXPERIMENTAL

Unrelated donor, single umbilical cord blood unit transplant; conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil

Biological: Single Umbilical Cord Blood Unit TransplantRadiation: Total Body IrradiationDrug: CyclophosphamideDrug: FludarabineDrug: Cyclosporine ADrug: Mycophenolate Mofetil

Double Cord Blood Transplant

EXPERIMENTAL

Unrelated donor, double umbilical cord blood unit transplant; Conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil

Biological: Double Umbilical Cord Blood Unit TransplantRadiation: Total Body IrradiationDrug: CyclophosphamideDrug: FludarabineDrug: Cyclosporine ADrug: Mycophenolate Mofetil

Interventions

Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF

Single Cord Blood Transplant

Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF

Double Cord Blood Transplant

The TBI will be delivered from either a linear accelerator or cobalt source at a dose rate of between 4 and 26 cGy/minute using energies of between 1 and 25 MV.

Also known as: TBI
Double Cord Blood TransplantSingle Cord Blood Transplant

Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush on Days -3 and -2.

Also known as: Cytoxan®
Double Cord Blood TransplantSingle Cord Blood Transplant

Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -10 through -8. Fludarabine will not be dose adjusted for body weight.

Also known as: Fludara
Double Cord Blood TransplantSingle Cord Blood Transplant

CSA will be administered beginning on Day -3 and doses will be adjusted to maintain a level of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods). CSA can be administered per institutional practice.

Also known as: CSA
Double Cord Blood TransplantSingle Cord Blood Transplant

MMF will be given at a dose of 1 gram IV q 8 hours if \> 50 kg or 15 mg/kg IV q 8 hours if \< 50 kg beginning the morning of Day -3.

Also known as: MMF, Cellcept®
Double Cord Blood TransplantSingle Cord Blood Transplant

Eligibility Criteria

Age1 Year - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Two partially HLA-matched UCB units. Units must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing) loci with the patient, and the units must be HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with each other (using same resolution of molecular typing as indicated above). Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved nucleated cell dose of at least 2.5 x 10\^7 per kilogram and the second unit at least 1.5 x 10\^7 per kilogram.
  • Acute myelogenous leukemia (AML) at the following stages:
  • High risk first complete remission (CR1), defined as the following:
  • Having preceding myelodysplasia (MDS)
  • High risk cytogenetics (high risk cytogenetics: del (5q) -5, -7, abn (3q), t (6;9) complex karyotype \[at least 5 abnormalities\],)the presence of a high FLT3 ITD-AR (\> 0.4)
  • Requiring more than 1 cycle of chemotherapy to obtain complete remission (CR);
  • FAB M6
  • Second or greater CR
  • First relapse with less than 25% blasts in bone marrow
  • Morphologic complete remission with incomplete blood count recovery
  • Therapy-related AML for which prior malignancy has been in remission for at least 12 months
  • Acute lymphocytic leukemia (ALL) at the following stages:
  • High risk first remission, defined as one of the following conditions:
  • Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL)
  • Mixed lineage leukemia (MLL) rearrangement with slow early response (defined as having M2 \[5-25% blasts\] or M3 \[more than 25% blasts on bone marrow examination on Day 14 of induction therapy\])
  • +23 more criteria

You may not qualify if:

  • Pregnant (β-positive human chorionic gonadotropin \[HCG\]) or breastfeeding
  • Evidence of HIV infection or HIV positive serology
  • Current uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms)
  • Autologous transplant less than 12 months prior to enrollment
  • Prior autologous transplant for the disease for which the UCB transplant will be performed
  • Prior allogeneic hematopoietic stem cell transplant
  • Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment
  • Inability to receive TBI
  • Requirement of supplemental oxygen
  • HLA-matched related donor able to donate

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (38)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Childrens Hospital at Oakland

Oakland, California, 94609, United States

Location

UCSD/Rady Childrens Hospital

San Diego, California, 92123, United States

Location

University of California, San Francisco (Peds)

San Francisco, California, 94143, United States

Location

The Children's Hospital of Denver

Denver, Colorado, 80218, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida College of Medicine (Shands)

Gainesville, Florida, 32610, United States

Location

Nemours Childrens Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33710, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322-1062, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

University of Louisville/Kosiar Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Children's of New Orleans

New Orleans, Louisiana, 70118, United States

Location

DFCI/Children's Hospital of Boston

Boston, Massachusetts, 02115, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute/Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64108, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-7610, United States

Location

Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

Location

Cook Childrens Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Utah BMT/University of Utah Medical School

Salt Lake City, Utah, 84132, United States

Location

Virgina Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E3, Canada

Location

Related Publications (2)

  • Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Thomas ED. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980 Aug;69(2):204-17. doi: 10.1016/0002-9343(80)90380-0.

    PMID: 6996481BACKGROUND
  • Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, Walters M, Horowitz MM, Kurtzberg J; Blood and Marrow Transplant Clinical Trials Network. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014 Oct 30;371(18):1685-94. doi: 10.1056/NEJMoa1405584.

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMyelodysplastic SyndromesLymphoma

Interventions

Whole-Body IrradiationCyclophosphamidefludarabinefludarabine phosphateCyclosporineMycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesMyeloproliferative DisordersBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsInvestigative TechniquesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipids

Results Point of Contact

Title
Adam Mendizabal
Organization
The EMMES Corporation

Study Officials

  • Mary Horowitz, MD, MS

    Center for International Blood and Marrow Transplant Research

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 14, 2006

First Posted

December 18, 2006

Study Start

December 1, 2006

Primary Completion

March 1, 2014

Study Completion

October 1, 2014

Last Updated

October 28, 2021

Results First Posted

December 21, 2015

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

Findings were published in a manuscript.

Time Frame
Within 6 months of official study closure at participating sites.
Access Criteria
Available to the public.
More information

Locations