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Donor Umbilical Cord Blood Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

3. března 2011 aktualizováno: Roswell Park Cancer Institute

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

RATIONALE: 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 allogeneic umbilical cord blood transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Spojené státy
    • California
      • Duarte, California, Spojené státy, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, Spojené státy, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, Spojené státy, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, Spojené státy, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, Spojené státy, 94143-1278
        • Children's Medical Center, University of California San Francisco
    • District of Columbia
      • Washington, District of Columbia, Spojené státy, 20010-2970
        • Children's National Medical Center
    • Indiana
      • Indianapolis, Indiana, Spojené státy, 46202-5289
        • Indiana University Cancer Center
    • Louisiana
      • New Orleans, Louisiana, Spojené státy, 70118
        • Children's Hospital of New Orleans
    • Massachusetts
      • Boston, Massachusetts, Spojené státy, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, Spojené státy, 49503
        • Spectrum Health and DeVos Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, Spojené státy, 55455
        • University of Minnesota Cancer Center
    • Missouri
      • Kansas City, Missouri, Spojené státy, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, Spojené státy, 63104-1095
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, Spojené státy, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, Spojené státy, 14263-0001
        • Roswell Park Cancer Institute
      • Manhasset, New York, Spojené státy, 11030
        • North Shore University Hospital
      • Rochester, New York, Spojené státy, 14642
        • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • North Carolina
      • Durham, North Carolina, Spojené státy, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, Spojené státy, 44106-5065
        • Ireland Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Spojené státy, 15213
        • Children's Hospital of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, Spojené státy, 37232-6310
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, Spojené státy, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, Spojené státy, 75235
        • Children's Medical Center of Dallas
      • San Antonio, Texas, Spojené státy, 78229
        • Texas Transplant Institute
    • Washington
      • Seattle, Washington, Spojené státy, 98109-1024
        • Fred Hutchinson Cancer Research Center

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

Ne starší než 17 let (Dítě)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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)

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Maskování: Žádné (otevřený štítek)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Roswell Park Cancer Institute

Spolupracovníci

National Heart, Lung, and Blood Institute (NHLBI)

Vyšetřovatelé

  • Studijní židle: Philip L. McCarthy, MD, Roswell Park Cancer Institute

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. ledna 2003

Primární dokončení (Aktuální)

1. září 2003

Dokončení studie (Aktuální)

1. září 2005

Termíny zápisu do studia

První předloženo

6. března 2003

První předloženo, které splnilo kritéria kontroly kvality

6. března 2003

První zveřejněno (Odhad)

7. března 2003

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

7. března 2011

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

3. března 2011

Naposledy ověřeno

1. března 2011

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • CDR0000270487
  • RPCI-DS-00-22

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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