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Unrelated Umbilical Cord Blood As An Alternate Source Of Stem Cells Transplantation


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

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Trial Information

Unrelated Umbilical Cord Blood As An Alternate Source Of Stem Cells Transplantation


OBJECTIVES:

- Determine 180-day survival in patients with malignant or nonmalignant hematologic
diseases treated with allogeneic umbilical cord blood transplantation. (Severe aplastic
anemia, Fanconi anemia, and marrow failure syndromes strata are closed to accrual;
adult [over 18 years of age] patient stratum is closed to accrual.)

- Determine disease-free and long-term survival in patients treated with this regimen.

- Determine the incidence of neutrophil engraftment, primary and secondary graft failure,
platelet engraftment, and red blood cell engraftment in patients treated with this
regimen.

- Determine the incidence and severity of acute and chronic graft-versus-host disease in
patients treated with this regimen.

- Determine the incidence of complications, including infection, veno-occlusive disease,
and interstitial pneumonitis, in patients treated with this regimen.

- Determine the incidence of 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 grouped according to the following
strata:

- Stratum I: Malignant disease, 5/6 or 6/6 HLA match, age 18 and under

- Stratum II: Malignant disease, 4/6 HLA match, age 18 and under

- Stratum III: Malignant disease, 3/6 HLA match, age 18 and under

- Stratum IV: Malignant disease, 2/6 or 1/6 HLA match, age 18 and under

- Stratum V (closed to accrual): Severe aplastic anemia, Fanconi anemia, or other marrow
failure syndrome

- Stratum VI: Inborn errors of metabolism/storage diseases and other nonmalignant
diseases not included in stratum V

- Stratum VII: Malignant disease receiving alternative conditioning regimen comprising
busulfan and melphalan

- Stratum VIII (closed to accrual): Adult patients (over age 18)

- Conditioning therapy: Patients are assigned to 1 of 5 groups according to diagnosis.

- Group I (malignant disease or severe aplastic anemia [severe aplastic anemia
closed to accrual]): Patients undergo total body irradiation (TBI) once or twice
daily on days -8 to -4. Patients then receive cyclophosphamide IV on days -3 and
-2, methylprednisolone IV on days -3 to 0, and antithymocyte globulin (ATG) IV
once or twice daily on days -3 to -1.

- Group II (Fanconi anemia [closed to accrual]): Patients undergo TBI on day -6, and
then receive cyclophosphamide IV and fludarabine IV on days -5 to -2, and
methylprednisolone IV and ATG IV on days -5 to -1.

- Group III (inborn errors of metabolism/storage disease): Patients receive oral
busulfan 4 times daily on days -9 to -6, cyclophosphamide as in group II, and
methylprednisolone and ATG as in group I.

- Group IV (other nonmalignant diseases): Patients receive conditioning therapy as
in group III. Patients with familial erythrophagocytic lymphohistiocytosis or
Langerhans cell histiocytosis also receive etoposide on days -5 to -3.

- Group V (non-TBI regimen for leukemia patients under 2 years of age): Patients
receive oral busulfan 4 times daily on days -8 to -5, melphalan IV on days -4 to
-2, and methylprednisolone and ATG as in group I.

- Allogeneic umbilical cord blood transplantation: All patients undergo umbilical cord
blood transplantation on day 0. Beginning on day 0 or 1, patients receive filgrastim
(G-CSF) IV or subcutaneously daily until blood counts recover.

- Graft-versus-host disease prophylaxis: Patients receive cyclosporine (IV or oral)
beginning between days -3 and -1 and continuing for 1 year after transplantation and
methylprednisolone twice daily beginning on day 1 and continuing until blood counts
recover.

Patients are followed weekly for 14 weeks, at 100 days, and at 4, 5, 6, 9, 12, 18, 24, and
36 months.

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following hematologic malignancies:

- Acute myeloid leukemia (AML)*

- With or without history of myelodysplastic syndromes (MDS)

- Patients in first complete remission (CR) (no greater than 5% blasts in
marrow) with translocations t(8;21) and inv(16) are allowed provided they
failed first-line induction therapy

- Patients in first CR (no greater than 5% blasts in marrow) with
translocations t(15;17) are allowed provided at least 1 of the following is
true:

- Failed first-line induction therapy

- Molecular evidence of persistent disease

- No patients in first CR and with Down syndrome

- Acute lymphoblastic leukemia (ALL)*, meeting 1 of the following criteria:

- Not in first CR (no greater than 5% blasts in marrow)

- In first CR and high risk as defined by 1 of the following:

- Hypoploidy (no more than 44 chromosomes)

- Pseudodiploidy with translocations or molecular evidence of t(9;22),
11q23, or t(8;14) (excluding B-ALL) or +MLL gene rearrangement

- One of the following elevated WBC levels:

- WBC greater than 100,000/mm^3 if 6 to 12 months of age

- WBC greater than 200,000/mm^3 if between 10 and 17 years of age

- WBC greater than 20,000/mm^3 if 18 years of age and over (adult
[over 18 years of age] patient stratum closed to accrual)

- Failed to achieve CR after 4 weeks of induction therapy

- B-ALL that is not in first CR or that meets at least 1 of the high-risk
criteria specified above

- No translocation t(8;14)

- No blasts with surface immunoglobulins

- CD10 negative

- Undifferentiated leukemia*

- Infant leukemia*

- Biphenotypic leukemia*

- Chronic myelogenous leukemia, meeting 1 of the following criteria:

- Accelerated phase

- Chronic phase

- At least 1 year from diagnosis without an identified matched unrelated
bone marrow donor AND unresponsive to or unable to tolerate interferon

- Blast crisis* (greater than 30% promyelocytes plus blasts in the marrow)

- One of the following MDS:

- Refractory anemia

- Refractory anemia with ringed sideroblasts

- Refractory anemia with excess blasts (RAEB)

- RAEB in transformation

- Chronic myelomonocytic leukemia

- Paroxysmal nocturnal hemoglobinuria

- Hodgkin's or non-Hodgkin's lymphoma beyond first CR or failed primary induction
therapy

- Tumor displays chemosensitivity (greater than 50% reduction in mass size
after the most recent therapy) NOTE: *Patients in third or greater
medullary relapse or refractory disease (other than primary induction
failures) or blast crisis receive the study busulfan/melphalan conditioning
regimen)

OR

- Diagnosis of one of the following nonmalignant diseases :

- Acquired severe aplastic anemia (stratum closed to accrual)

- Unresponsive to medical therapy with anti-thymocyte globulin and/or
cyclosporine

- Inborn errors of metabolism, including, but not limited to the following:

- Hurler's syndrome

- Adrenoleukodystrophy

- Maroteaux-Lamy syndrome

- Globoid cell leukodystrophy

- Metachromatic leukodystrophy

- Fucosidosis

- Mannosidosis

- Fanconi anemia documented by increased chromosomal fragility assays and meeting
1 of the following criteria (stratum closed to accrual):

- Severe pancytopenia

- Absolute neutrophil count less than 500/mm^3

- Platelet count less than 20,000/mm^3

- Hemoglobin less than 8 g/dL

- Morphologic evidence of MDS with clonal chromosomal abnormalities

- Leukemia transformation

- Other marrow failure syndromes, including any of the following (stratum closed
to accrual):

- Blackfan-Diamond syndrome that is unresponsive to medical therapy

- Kostmann's congenital agranulocytosis unresponsive to medical therapy

- Congenital amegakaryocytic thrombocytopenia

- Thrombocytopenia absent radius

- Combined immune deficiencies including, but not limited to the following:

- Severe combined immunodeficiency (SCID)

- 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

- Nezeloff's syndrome

- Cartilage hair hypoplasia

- Reticular dysgenesis

- No active CNS leukemia (cerebrospinal fluid with WBC greater than 5/mm^3 and
malignant cells on cytospin)

- No SCID patients who do not require cytoreduction

- No dyskeratosis congenita

- No primary myelofibrosis

- No grade 3 or greater myelofibrosis

- Familial erythrophagocytic lymphohistiocytosis patients must not have any of the
following:

- Abnormal brain MRI

- Neurologic symptoms

- Lymphocytes and monocytes greater than 7/mm^3 in the cerebrospinal fluid

- No available 5/6 or 6/6 HLA-matched related donor

PATIENT CHARACTERISTICS:

Age

- 55 and under (over 18 closed to accrual)

Performance status

- Karnofsky 70-100% OR

- Lansky 50-100% (patients under 16 years old)

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- SGOT less than 5 times upper limit of normal

- Bilirubin less than 2.5 mg/dL

Renal

- Creatinine normal for age OR

- Creatinine clearance or glomerular filtration rate greater than 50% of lower limit of
normal

Cardiovascular

- LVEF greater than 40% at rest and must improve with exercise* OR

- Shortening fraction greater than 26%* NOTE: *If symptomatic

Pulmonary

- DLCO greater than 45% of predicted* (corrected for hemoglobin)

- FEV_1 and FEC greater than 45% of predicted (corrected for hemoglobin) OR

- Room air oxygen saturation greater than 85%* NOTE: *If symptomatic

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled viral, bacterial, or fungal infection

- HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- More than 12 months since prior allogeneic stem cell transplantation with
cytoreductive preparative therapy

- More than 6 months since prior autologous stem cell transplantation

Chemotherapy

- See Biologic therapy

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- No prior enrollment on this study

- No continuous life support (e.g., mechanical ventilation) within 1 year after study
transplantation (for patients with inborn errors of metabolism)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Philip L. McCarthy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000270487

NCT ID:

NCT00055653

Start Date:

January 2003

Completion Date:

September 2005

Related Keywords:

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic-Myeloproliferative Diseases
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • refractory anemia with ringed sideroblasts
  • refractory anemia
  • chronic myelomonocytic leukemia
  • childhood acute myeloid leukemia in remission
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • childhood acute lymphoblastic leukemia in remission
  • recurrent childhood acute lymphoblastic leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • acute undifferentiated leukemia
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • untreated childhood acute lymphoblastic leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
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
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
North Shore University HospitalManhasset, New York  11030
Hackensack University Medical CenterHackensack, New Jersey  07601
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
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Children's Medical Center of DallasDallas, Texas  75235
Texas Transplant InstituteSan Antonio, Texas  78229
Children's Medical Center, University of California San FranciscoSan Francisco, California  94143-1278