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A Multicenter Study of Unrelated Umbilical Cord Blood as an Alternate Source of Stem Cells for Transplantation


Phase 2
N/A
18 Years
Not Enrolling
Both
Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

A Multicenter Study of Unrelated Umbilical Cord Blood as an Alternate Source of Stem Cells for Transplantation


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Colleen Delaney, MD, MSC

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1330.00

NCT ID:

NCT00003913

Start Date:

December 1998

Completion Date:

August 2005

Related Keywords:

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • 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
  • Hematologic Diseases
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Ireland Cancer CenterCleveland, Ohio  44106-5065
Medical City Dallas HospitalDallas, Texas  75230
North Shore University HospitalManhasset, New York  11030
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Spectrum Health and DeVos Children's HospitalGrand Rapids, Michigan  49503
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Warren Grant Magnuson Clinical CenterBethesda, Maryland  20892-1182
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182