Single Versus Double Umbilical Cord Blood Transplantation in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00412360
First received: December 14, 2006
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Myelodysplastic Syndrome
NK Cell Lymphoblastic Leukemia
Biological: Single Cord Blood Unit Transplantation
Biological: Double Cord Blood Unit Transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-center, Open Label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia (BMT CTN #0501)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Neutrophil engraftment [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Chimerism [ Time Frame: 28, 42, 60, 180, 365 days ] [ Designated as safety issue: No ]
  • Acute graft-versus-host disease (GVHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Transplant-related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Infections [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Immune reconstitution [ Time Frame: 100 days, 6 months, 1 and 2 years ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Platelet engraftment [ Time Frame: 100 days, 6 months, 1 year ] [ Designated as safety issue: No ]
  • Graft failure [ Time Frame: 42 days, 100 days ] [ Designated as safety issue: Yes ]

Enrollment: 224
Study Start Date: December 2006
Estimated Study Completion Date: May 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Single Cord Blood Unit Transplantation
Biological: Single Cord Blood Unit Transplantation
Unrelated donor, single cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
Experimental: 2
Double Cord Blood Unit Transplantation
Biological: Double Cord Blood Unit Transplantation
Unrelated donor, double cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF

Detailed Description:

BACKGROUND:

In nearly every large single center or registry analysis of outcomes after UCB transplantation, cell dose is identified as an important factor influencing the incidence and rate of hematopoietic recovery, risk of transplant-related mortality, and probability of survival. Pilot data suggest that infusion of two partially human leukocyte antigen (HLA)-matched UCB units, which always augments the graft cell dose, is safe and may improve neutrophil recovery and survival. To determine whether the infusion of two UCB units enhances survival, a multi-center, open-label, randomized trial is proposed. As adequate single UCB units can be identified for more than 80% of pediatric recipients (in contrast to less than 30% for adults), this study will be open only to pediatric patients. The population will be restricted to patients with high-risk hematologic malignancy, the most common indication of UCB transplantation in children.

DESIGN NARRATIVE:

Participants will include patients 1 to 21 years of age with a diagnosis of hematological malignancy and with two partially HLA-matched UCB units. Units must be HLA-matched at 3 of 6 HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) with each other and 4 of 6 with the recipient. 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 delivers at least 1.5 x 10^7 per kilogram.

Patients will be randomized no more than 14 days prior to initiation of conditioning. UCB units will be shipped prior to initiation of conditioning.

The preparative regimen will consist of the following:

  • Fludarabine: 25 mg/m2/day IV on Days -10, -9, and -8.
  • Total Body Irradiation (TBI): 165 cGy twice daily on Days -7, -6, -5, and -4.
  • Cyclophosphamide: 60 mg/kg/day x 2 on Days -3 and -2.
  • Day 0 will be the day of the UCB transplant. The GVHD prophylaxis regimen will be mycophenolate mofetil (MMF) 15 mg/kg IV BID on Day -3 to Day + 45 and cyclosporine A (CSA) to maintain level 200-400 ng/mL beginning on Day -3.

Patients will be followed for at least 24 months post-transplant.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. 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
    2. Second or greater CR
    3. First relapse with less than 25% blasts in bone marrow
    4. 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:

    1. 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])
      • Hypodiploidy (less than 44 chromosomes or DNA index less than 0.81)
      • End of induction M3 bone marrow
      • End of induction M2 with M2-3 at Day 42
      • Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction.
    2. High risk second remission, defined as one of the following conditions:

      • Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL)
      • Bone marrow relapse less than 36 months from induction
      • T-lineage relapse at any time
      • Very early isolated central nervous system (CNS) relapse (6 months from diagnosis)
      • Slow reinduction (M2-3 at Day 28) after relapse at any time
      • Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction.
    3. Any third or subsequent CR
  • NK cell lymphoblastic leukemia in any CR
  • Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow (BM)
  • Myelodysplastic syndrome (MDS) at any stage
  • Chronic myelogenous leukemia (CML) in chronic or accelerated phase
  • All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
  • Patients 16 years old or older must have a Karnofsky score of at least 70% and patients younger than 16 years old must have a Lansky score of at least 70%.
  • Patients with adequate physical function as measured by:

    1. Cardiac: Left ventricular ejection fraction greater than 40% or shortening fraction greater than 26%
    2. Hepatic: Bilirubin no more than 2.5 mg/dL; ALT, AST and ALP no more than 5 times the upper limit of normal (ULN)
    3. Renal: Serum creatinine within normal range for age, or if serum creatinine is outside normal range for age, then renal function (creatinine clearance or GFR) greater than 70 mL/min/1.73 m^2
    4. Pulmonary: DLCO, FEV1, FEC (diffusion capacity) greater than 50% of predicted value (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation greater than 92% of room air

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412360

  Hide Study Locations
Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Childrens Hospital at Oakland
Oakland, California, United States, 94609
UCSD/Rady Childrens Hospital
San Diego, California, United States, 92123
University of California, San Francisco (Peds)
San Francisco, California, United States, 94143
United States, Colorado
The Children's Hospital of Denver
Denver, Colorado, United States, 80218
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida College of Medicine (Shands)
Gainesville, Florida, United States, 32610
Nemours Childrens Clinic
Jacksonville, Florida, United States, 32207
University of Miami
Miami, Florida, United States, 33136
All Children's Hospital
St. Petersburg, Florida, United States, 33710
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322-1062
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Louisville/Kosiar Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Children's of New Orleans
New Orleans, Louisiana, United States, 70118
United States, Massachusetts
DFCI/Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute/Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi
Jackson, Mississippi, United States, 39216
United States, Missouri
Children's Mercy Hospital and Clinics
Kansas City, Missouri, United States, 64108
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2696
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-7610
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
Cook Childrens Medical Center
Forth Worth, Texas, United States, 76104
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Utah
Utah BMT/University of Utah Medical School
Salt Lake City, Utah, United States, 84132
United States, Virginia
Virgina Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53211
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Canada, British Columbia
BC Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E3
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
Principal Investigator: Joseph Rosenthal, MD City of Hope National Medical Center
Principal Investigator: Terry Fry, MD Children's Research Institute
Principal Investigator: John Wingard, MD University of Florida College of Medicine (Shands)
Principal Investigator: Aleksandra Petrovic, MD All Children’s Hospital Johns Hopkins Medicine
Principal Investigator: Paul Haut, MD Indiana University School of Medicine
Study Chair: John Wagner, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Shalini Shenoy, MD Washington University, St. Louis Children's Hospital
Principal Investigator: Alfred Grovas, MD University of Nebraska
Principal Investigator: Joel Brochstein, MD Hackensack University Medical Center
Principal Investigator: Andromachi Scaradavou, MD Memorial Sloan-Kettering Cancer Center
Study Chair: Joanne Kurtzberg, MD Duke University
Principal Investigator: Colleen Delaney, MD Fred Hutchinson Cancer Research Center
Principal Investigator: Mason Bond, MD British Columbia Cancer Agency
Principal Investigator: Roger Giller, MD The Children's Hospital of Denver
Principal Investigator: Nancy Bunin, MD Children's Hospital of Philadelphia
Principal Investigator: Victor Aquino, MD Children's Medical Center Dallas
Principal Investigator: Jignesh Dalal, MD Children's Mercy Hospital and Clinics
Principal Investigator: Lolie Yu, MD Children's of New Orleans
Principal Investigator: Leslie Lehmann, MD DFCI/Children's Hospital of Boston
Principal Investigator: Dave Margolis, MD Medical College of Wisconsin
Principal Investigator: Eneida Nemecek, MD Oregon Health and Science University
Principal Investigator: Michael Grimley, MD Texas Transplant Institute
Principal Investigator: Alexa Cheerva, MD University of Louisville/Kosiar Children's Hospital
Principal Investigator: Edward Peres, MD University of Michigan
Principal Investigator: Michael Pulsipher, MD Utah BMT/University of Utah Medical School
Principal Investigator: John Horan, M.D., M.P.H Children's Healthcare of Atlanta
Principal Investigator: Peter John Shaw, C.A. Children's Hospital at Westmead
Principal Investigator: Mark Walters, M.D. Children's Hospital at Oakland
Principal Investigator: Gretchen Eames, M.D. Cook Children's Medical Center
Principal Investigator: Michel Duval Hopital Sainte-Justine
Principal Investigator: Roland Chu, M.D. Karmanos/Children's Hospital of Michigan
Principal Investigator: Theodore Moore, M.D. Mattel Children's Hospital at UCLA
Principal Investigator: David Margolis, M.D. Medical College of Wisonsin
Principal Investigator: Luciano JM Costa, M.D., Ph.D Medical University of South Carolina
Principal Investigator: Amanda Termuhlen, M.D. Nationwide Children's Hospital
Principal Investigator: Eric Sandler, M.D. Nemours Children's Clinic
Principal Investigator: Roberta H. Adams, M.D. Phoenix Children's Hospital
Principal Investigator: Martin Brecher, M. D. Roswell Park Cancer Institute
Principal Investigator: Draga Barbaric, M.D. Sydney Children's Hospital
Principal Investigator: Eric J Anderson, M.D. UCSD/Rady Childrens Hospital
Principal Investigator: Gary Kleiner, M.D. University of Miami
Principal Investigator: Gail C Megason, M.D. University of Mississippi Medical Center
Principal Investigator: Haydar Frangoul, M.D. Vanderbilt University
Principal Investigator: Kamar Godder, M.D. Virginia Commonwealth University
Principal Investigator: Mehmet F Ozkaynak, MD New York Medical College
Principal Investigator: Bilijana Horn, MD University of California, San Francisco (Peds)
  More Information

Additional Information:
No publications provided

Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00412360     History of Changes
Obsolete Identifiers: NCT00429598
Other Study ID Numbers: 467, 2U01HL069294
Study First Received: December 14, 2006
Last Updated: February 10, 2014
Health Authority: United States: Federal Government

Keywords provided by Medical College of Wisconsin:
Double cord blood

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on October 21, 2014