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Acute Myelogenous LeukemiaPhase 3NCT00412360

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

A Phase 3 study testing Single Umbilical Cord Blood Unit Transplant, Double Umbilical Cord Blood Unit Transplant and Total Body Irradiation in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Medical College of Wisconsin at 38 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Single Umbilical Cord Blood Unit Transplant, Double Umbilical Cord Blood Unit Transplant and Total Body Irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
224 participants
Where
38 sitesin 3 countries
Study dates
Dec 2006to Oct 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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);
Show all 38Show fewer
  • 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])
  • 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.
  • 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.
  • 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:
  • Cardiac: Left ventricular ejection fraction greater than 40% or shortening fraction greater than 26%
  • Hepatic: Bilirubin no more than 2.5 mg/dL; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) no more than 5 times the upper limit of normal (ULN)
  • 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
  • Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

38 sites in 3 countries.

38 sites in 3 countries

United States36 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322-1062

  • University of Alabama

    Birmingham, Alabama, 35294

  • DFCI/Children's Hospital of Boston

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Children's Medical Center of Dallas

    Dallas, Texas, 75235

  • The Children's Hospital of Denver

    Denver, Colorado, 80218

  • Karmanos Cancer Institute/Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Cook Childrens Medical Center

    Fort Worth, Texas, 76104

  • University of Florida College of Medicine (Shands)

    Gainesville, Florida, 32610

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • University of Mississippi

    Jackson, Mississippi, 39216

  • Nemours Childrens Clinic

    Jacksonville, Florida, 32207

  • Children's Mercy Hospital and Clinics

    Kansas City, Missouri, 64108

  • University of Louisville/Kosiar Children's Hospital

    Louisville, Kentucky, 40202

  • University of Miami

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53211

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-7610

  • Children's of New Orleans

    New Orleans, Louisiana, 70118

  • Childrens Hospital at Oakland

    Oakland, California, 94609

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Virgina Commonwealth University

    Richmond, Virginia, 23298

  • Utah BMT/University of Utah Medical School

    Salt Lake City, Utah, 84132

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • UCSD/Rady Childrens Hospital

    San Diego, California, 92123

  • University of California, San Francisco (Peds)

    San Francisco, California, 94143

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • All Children's Hospital

    St. Petersburg, Florida, 33710

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Australia1 site

  • Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

Canada1 site

  • BC Cancer Agency

    Vancouver, British Columbia, V5Z 4E3

Other trials in Canada

About this study

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)

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.

Read the 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 Graft-vs-Host-Disease (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.

Being tested
Single Umbilical Cord Blood Unit Transplant, Double Umbilical Cord Blood Unit Transplant, Total Body Irradiation, Cyclophosphamide, Fludarabine
Keywords
Double cord blood
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Single Umbilical Cord Blood Unit TransplantBiological

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

  • Double Umbilical Cord Blood Unit TransplantBiological

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

  • Total Body IrradiationRadiation

    Also called TBI

    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.

  • CyclophosphamideDrug

    Also called Cytoxan®

    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.

  • FludarabineDrug

    Also called Fludara

    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.

  • Cyclosporine ADrug

    Also called CSA

    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.

  • Mycophenolate MofetilDrug

    Also called MMF, Cellcept®

    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.

Study groups in NCT00412360
Study groupRoleWhat they receive
Single Cord Blood TransplantExperimentalUnrelated donor, single umbilical cord blood unit transplant; conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil
Receives: Biological: Single Umbilical Cord Blood Unit Transplant; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil
Double Cord Blood TransplantExperimentalUnrelated donor, double umbilical cord blood unit transplant; Conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil
Receives: Biological: Double Umbilical Cord Blood Unit Transplant; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Overall Survival

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

    Measured: 1 year post-randomization

Secondary outcomes (9)

  1. Percentage of Participants With Disease-free Survival

    Disease-free survival is defined as survival without relapse of the primary disease.

    Measured: 1 year post-randomization

  2. Percentage of Participants With Neutrophil and Platelet Engraftment

    Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 50,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

    Measured: Days 42 and 100

  3. Time to Neutrophil and Platelet Engraftment

    Platelet engraftment is defined as achieving platelet counts greater than 50,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

    Measured: 2 years post-transplant

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

    Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

    Skin stage:

    0: No rash

    1. Rash <25% of body surface area
    2. Rash on 25-50% of body surface area
    3. Rash on > 50% of body surface area
    4. Generalized erythroderma with bullous formation

    Liver stage (based on bilirubin level)*:

    0: <2 mg/dL

    1. 2-3 mg/dL
    2. 3.01-6 mg/dL
    3. 6.01-15.0 mg/dL
    4. >15 mg/dL

    GI stage*:

    0: No diarrhea or diarrhea <500 mL/day

    1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
    2. Diarrhea 1000-1499 mL/day
    3. Diarrhea >1500 mL/day
    4. Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

    GVHD grade:

    0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

    Measured: Day 100 post-randomization

  5. Percentage of Participants With Chronic GVHD

    Incidences of chronic GVHD will be graded per Shulman et al. 1980. This reference categorizes chronic GVHD as either limited or extensive. For this outcome, participants developing either type are considered to have a chronic GVHD event.

    Measured: 1 year post-randomization

  6. Number of Infections Per Participant

    Measured: 2 years post-randomization

  7. Percentage of Participants With Relapse

    Relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, or MDS consistent with pre-transplant features. Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation.

    Measured: 1 year post-randomization

  8. Percentage of Participants With Treatment-related Mortality

    Treatment related mortality is defined as death without relapse of the primary disease.

    Measured: 1 year post-randomization

  9. Number of Participants With Engraftment Syndrome

    Measured: Day 100 post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2006 (estimated)
  2. Study startDec 2006
  3. Primary completionMar 2014
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
224 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00412360
Sponsor's protocol ID
BMTCTN0501
Other IDs
2U01HL069294, 5U24CA076518
Status last verified
Oct 2021
First submitted
14 Dec 2006
Last updated
28 Oct 2021
Data monitoring committee
Yes
Individual data sharing
Yes: Findings were published in a manuscript.

Publications

  • 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.

    PubMed 6996481

  • 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.

    PubMed 25354103

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Single Umbilical Cord Blood Unit Transplant, Double Umbilical Cord Blood Unit Transplant and Total Body Irradiation in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Medical College of Wisconsin at 38 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Overall Survival (time frame: 1 year post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00412360, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.

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