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CompletedNCT00003913Updated Apr 2, 2010

Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Nonmalignant Hematologic Disease

A Phase 2 interventional study of anti-thymocyte globulin and filgrastim in Leukemia, Lymphoma and Myelodysplastic Syndromes, sponsored by Fred Hutchinson Cancer Center. Completed at 23 sites in United States. Open to participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2010-04-02.

Sponsored by Fred Hutchinson Cancer Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
390
Ages
Up to 18 Years
Sex
All
01

Study summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation plus combination chemotherapy in treating patients who have hematologic cancer or nonmalignant hematologic disease.

Read the detailed description

OBJECTIVES:

  • Determine the efficacy of umbilical cord blood transplantation, as measured by durable neutrophil engraftment, in patients with malignant or nonmalignant hematological disease.
  • Determine the disease-free survival and long-term survival in patients treated with this regimen.
  • Determine the incidence of neutrophil engraftment, primary and secondary graft failure, platelet engraftment, and RBC engraftment in patients treated with this regimen.
  • Determine the incidence and severity of acute and chronic graft-versus-host disease, complications (infection, veno-occlusive disease, interstitial pneumonitis), relapse, other malignancies, lymphoproliferative disorders, and posttransplantation myelodysplasia in patients treated with this regimen.
  • Determine the immune reconstitution in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to disease group (malignant vs nonmalignant). Patients with malignant disease are further stratified according to quality of HLA match (1 or 2/6 vs 3/6 vs 4/6 vs 5/6 or 6/6), cell dose, and age.

Patients are assigned to one of three conditioning regimens, depending on disease.

  • Group A (malignant disease ): Patients undergo total body irradiation (TBI) once on day -8 and twice daily on days -7 to -4. Male patients with acute lymphocytic leukemia (ALL) undergo radiotherapy boost to testes. Patients receive cyclophosphamide (CTX) IV on days -3 and -2 and methylprednisolone (MePRDL) IV and anti-thymocyte globulin (ATG) IV on days -3 to -1.
  • Group B (inborn errors of metabolism/storage disease): Patients receive oral busulfan (BU) every 6 hours on days -6 and -5, CTX IV on days -4 and -3, and MePRDL IV and ATG IV every 12 hours on days -2 and -1.
  • Group C (other nonmalignant diseases): Patients receive oral BU every 6 hours on days -9 to -6, CTX IV on days -5 to -2, and MePRDL IV and ATG IV on days -3 to -1.

Patients in all groups receive cord blood IV over a maximum of 30 minutes on day 0. Patients also receive MePRDL IV with the first half of the infusion administered immediately before the cord blood infusion and filgrastim (G-CSF) IV beginning 4 hours after transplantation and continuing until blood counts recover.

Patients are followed at 30, 60, and 90 days; at 6 months; and then annually thereafter.

PROJECTED ACCRUAL: Approximately 390 patients will be accrued for this study within 5 years.

02

Conditions studied

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases

Keywords

  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • relapsing chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • childhood acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • recurrent/refractory childhood Hodgkin lymphoma
  • refractory anemia
  • refractory anemia with ringed sideroblasts
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • chronic myelomonocytic leukemia
  • acute undifferentiated leukemia
  • secondary acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • juvenile myelomonocytic leukemia
  • blastic phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's planned enrollment of 390 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.

Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Acute myeloid leukemia (AML), with or without myelodysplastic syndromes

      • Not in first complete remission (CR)* with translocations t(8;21) and inv (16) unless failure of first-line induction therapy
      • Not in first CR* with translocations t(15;17) abnormality unless:

        • Failure of first-line induction therapy OR
        • Molecular evidence of persistent disease
      • Not in first CR with Down syndrome
      • Patients with third or greater medullary relapse or refractory disease (other than primary induction failures) receive busulfan/melphalan conditioning regimen NOTE: * CR defined by no greater than 5% blasts in marrow
    • Acute lymphocytic leukemia (ALL)

      • Not in first CR OR
      • High-risk ALL in first CR, with high risk defined as one of the following:

        • Hypoploidy (no greater than 44 chromosomes)
        • Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14) (except B-cell ALL) with or without MLL gene arrangement
        • Elevated WBC at presentation

          • Age 6-12 months: greater than 100,000/mm\^3
          • Age 10-17 years: greater than 200,000/mm\^3
          • Age 18: greater than 20,000/mm\^3
        • Failed to achieve CR after 4 weeks of induction therapy
      • Patients with B-ALL must not be in first CR, must meet at least one of the high-risk criteria specified above, or must not meet any of the following criteria:

        • Translocation t(8;14)
        • Blasts have surface immunoglobulins
        • CD10 positive
      • Patients with third or greater medullary relapse or refractory disease (other than primary induction failures) receive busulfan/melphalan conditioning regimen
    • Chronic myelogenous leukemia, meeting criteria for 1 of the following:

      • Accelerated phase
      • Chronic phase if 1 year from diagnosis without a matched unrelated bone marrow donor AND unresponsive to or unable to tolerate interferon
      • Blast crisis, defined as greater than 30% promyelocytes plus blasts in bone marrow

        • Patients receive busulfan/melphalan conditioning regimen
    • Acute undifferentiated leukemia (AUL), infant leukemia, or biphenotypic leukemia

      • Patients with third or greater medullary relapse or refractory disease (other than primary induction failures) receive busulfan/melphalan conditioning regimen
    • Juvenile myelomonocytic leukemia meeting the following criteria:

      • No Philadelphia chromosome
      • Bone marrow blasts less than 30%
      • Peripheral blood monocytes greater than 1,000/mm\^3
      • At least 2 of the following:

        • Peripheral blood spontaneous growth and/or sargramostim (GM-CSF) hypersensitivity
        • Increased hemoglobin F for age
        • Clonal abnormalities (e.g., monosomy 7 or RAS mutations)
        • Peripheral blood with myeloid precursors
        • WBC greater than 10,000/mm\^3
    • Myelodysplastic syndromes defined by the following:

      • Refractory anemia (RA)
      • RA with ringed sideroblasts
      • RA with excess blasts (RAEB)
      • RAEB in transformation
      • Chronic myelomonocytic leukemia
    • Paroxysmal nocturnal hemoglobinuria
    • Hodgkin's lymphoma or non-Hodgkin's lymphoma beyond first CR or primary induction failures AND chemosensitive (greater than 50% reduction in tumor mass size)
    • Inborn error of metabolism including, but not limited to, Hurler's syndrome, adrenoleukodystrophy (ALD), Maroteaux-Lamy syndrome, globoid cell leukodystrophy, metachromatic leukodystrophy, fucosidosis, or mannosidosis

      • For ALD patients over age 5, IQ must be at least 80
      • For all other patients over age 5, IQ must be at least 70
      • For all patients age 5 and under, developmental quotient or clinical neurodevelopmental examination should demonstrate potential for stabilization at a level of functioning where continuous life support (e.g., mechanical ventilation) would not be predicted to be required in the year after transplantation
    • Combined immune deficiencies including, but not limited to:

      • Severe combined immunodeficiency (SCID) requiring cytoreduction
      • Wiskott-Aldrich syndrome
      • Leukocyte adhesion defect
      • Chediak-Higashi disease
      • X-linked lymphoproliferative disease
      • Adenosine deaminase deficiency
      • Purine nucleoside phosphorylase deficiency
      • X-linked SCID
      • Common variable immune deficiency
      • Nezelof's syndrome
      • Cartilage hair hypoplasia
  • No dyskeratosis congenita
  • No ALL, AML, AUL, or biphenotypic leukemia in third or higher medullary relapse or refractory disease other than primary induction failure
  • No primary myelofibrosis or myelofibrosis grade 3 or worse
  • No active CNS leukemia involvement (CSF with WBC greater than 5/mm\^3 and malignant cells on cytospin)
  • No consenting 5/6 or 6/6 HLA-matched related donor available
  • 3-6/6 HLA-matched unrelated umbilical cord blood donor available

PATIENT CHARACTERISTICS:

Age:

  • See Disease Characteristics
  • 18 and under

Performance status:

  • Karnofsky 70-100%, if age 16 to 18
  • Lansky 50-100%, if under age 16

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin less than 2.5 mg/dL
  • SGOT less than 5 times upper limit of normal

Renal:

  • Creatinine normal for age OR
  • Creatinine clearance or glomerular filtration rate greater than 50% lower limit of normal for age

Cardiovascular:

  • If symptomatic:

    • LVEF greater than 40% (or shortening fraction greater than 26%) and improves with exercise OR
    • Shortening fraction greater than 26%

Pulmonary:

  • If symptomatic:

    • DLCO, FEV_1, and FEC greater than 45% predicted OR
    • Oxygen saturation greater than 85% on room air

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No uncontrolled viral, bacterial, or fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • At least 1 year since prior allogeneic stem cell transplantation (SCT) with cytoreductive preparative therapy
  • At least 6 months since prior autologous SCT
  • No concurrent thrombopoietic growth factors

Chemotherapy:

  • See Disease Characteristics
  • See Biologic therapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Masking
None (open label)
Enrollment
390 participants (estimated)

Interventions

  • Biologicalanti-thymocyte globulin
  • Biologicalfilgrastim
  • Drugbusulfan
  • Drugcyclophosphamide
  • Drugmethylprednisolone
  • Procedureumbilical cord blood transplantation
  • Radiationradiation therapy
06

Study locations

23 sites
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010-3000, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90027-0700, United States
  • Jonsson Comprehensive Cancer Center, UCLA
    Los Angeles, California 90095-1781, United States
  • Children's Hospital of Orange County
    Orange, California 92868, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010-2970, United States
  • Indiana University Cancer Center
    Indianapolis, Indiana 46202-5289, United States
  • Children's Hospital of New Orleans
    New Orleans, Louisiana 70118, United States
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    Bethesda, Maryland 20892-1182, United States
  • Warren Grant Magnuson Clinical Center
    Bethesda, Maryland 20892-1182, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Spectrum Health and DeVos Children's Hospital
    Grand Rapids, Michigan 49503, United States
  • University of Minnesota Cancer Center
    Minneapolis, Minnesota 55455, United States
  • Children's Mercy Hospital
    Kansas City, Missouri 64108, United States
  • Cardinal Glennon Children's Hospital
    Saint Louis, Missouri 63104, United States
  • Cancer Center at Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • North Shore University Hospital
    Manhasset, New York 11030, United States
  • James P. Wilmot Cancer Center at University of Rochester Medical Center
    Rochester, New York 14642, United States
  • Duke Comprehensive Cancer Center
    Durham, North Carolina 27710, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
  • Ireland Cancer Center
    Cleveland, Ohio 44106-5065, United States
  • Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15213, United States
  • Medical City Dallas Hospital
    Dallas, Texas 75230, United States
  • Fred Hutchinson Cancer Research Center
    Seattle, Washington 98109, United States
07

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 2, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
08

Registry details

Key details

Study ID
NCT00003913
Lead sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)
First posted
Jan 27, 2003
Start date
Dec 1998
Primary completion
Aug 2005
Completion
Aug 2005
Last update
Apr 2, 2010

Study contacts

Colleen Delaney, MD, MSC
study chair · Fred Hutchinson Cancer Center
View the source record on ClinicalTrials.gov ↗

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