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

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003913
First received: November 1, 1999
Last updated: March 31, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: anti-thymocyte globulin
Biological: filgrastim
Drug: busulfan
Drug: cyclophosphamide
Drug: methylprednisolone
Procedure: umbilical cord blood transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Study of Unrelated Umbilical Cord Blood as an Alternate Source of Stem Cells for Transplantation

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Estimated Enrollment: 390
Study Start Date: December 1998
Study Completion Date: August 2005
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00003913

  Show 23 Study Locations
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Colleen Delaney, MD, MSC Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00003913     History of Changes
Obsolete Identifiers: NCT00053755
Other Study ID Numbers: 1330.00, FHCRC-1330.00, UMN-MT-9817, NCI-G99-1523, CDR0000067092
Study First Received: November 1, 1999
Last Updated: March 31, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
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
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

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Central Nervous System Agents
Hematologic Diseases
Leukemia
Lymphoma
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Lenograstim
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014