Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders

Sponsor
Fairview University Medical Center (Other)
Overall Status
Unknown status
CT.gov ID
NCT00006056
Collaborator
(none)
40
1

Study Details

Study Description

Brief Summary

OBJECTIVES: I. Determine the efficacy of unrelated donor hematopoietic stem cell transplantation in the treatment of patients with life threatening hemophagocytic disorders.

  1. Determine the rate of disease free survival, incidence of graft failure, and incidence of graft versus host disease in these patients after undergoing this treatment regimen.

Detailed Description

PROTOCOL OUTLINE: Patients receive oral busulfan twice a day on days -9 to -6; cyclophosphamide IV over 1 hour on days -5 to -2; etoposide IV over 4 hours on days -5 to -3; and anti-thymocyte globulin IV twice a day on days -2 and -1 and days 1 and 2. Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive graft versus host disease prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours (orally once the patients resumes eating) every 12 hours (every 8 hours for pediatric patients) starting on or prior to day -3 and continuing up to 1 year.

Patients are followed at days 28 and 100, at 6 months and 1 year, and then annually for 5 years.

Study Design

Study Type:
Interventional
Primary Purpose:
Treatment
Study Start Date :
Mar 1, 2000

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    0 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    PROTOCOL ENTRY CRITERIA:

    --Disease Characteristics--

    Patients diagnosed with any of the following active but stable, or nonactive/quiescent, hemophagocytic disorders:

    • Hemophagocytic lymphohistiocytosis (HLH)

    • Fever greater than 38.5 degrees Celsius

    • Splenomegaly (greater than 3 cm below costal margin)

    • Hemophagocytosis in bone marrow or spleen or lymph nodes

    • Disease may be confirmed by positive family history

    • No evidence of malignancy

    • Hypertriglyceridemia and/or hypofibrinogenemia

    • Fasting triglycerides at least 2.0 mmol/L or at least 3 standard deviations above normal for age

    • Fibrinogen no greater than 1.5 g/L or no greater than 3 standard deviations above normal

    • Cytopenia (affecting at least 2 of 3 lineages in the peripheral blood)

    • Hemoglobin less than 9.0 g/L

    • Platelet count less than 100,000/mm3

    X-linked lymphoproliferative disorder (XLP)

    Two or more maternally related males manifesting at least one of the following XLP phenotypes:

    • Fulminant infectious mononucleosis

    • Dysgammaglobulinemia

    • Malignant lymphoma/lymphoproliferative disorder

    • Aplastic anemia

    • Lymphoid granulomatosis/vasculitis OR

    • A maternally related male in an established XLP kindred who has strong genetic (RFLP) linkage to the XLP locus

    Chediak-Higashi syndrome

    Partial oculocutaneous albinism (hair, skin, eyes)

    Frequent bacterial infections

    Large peroxidase positive granules in leukocytes of peripheral blood or bone marrow

    Positive family history or parental consanguinity is supportive of the diagnosis

    May not have entered accelerated phase as defined by any of the following:
    • Lymphadenopathy

    • Pancytopenia

    • Histiocytes with hemophagocytosis in bone marrow, lymph nodes, liver, or spleen

    Viral associated hemophagocytic syndrome (VAHS)

    Relapsed after prior therapy or supportive care

    Diagnostic criteria as for HLH

    No hemophagocytic disorders secondary to underlying malignancy

    Patients 35 years of age and under must have a hematopoietic stem cell donor that is one of the following:

    • HLA A and B identical OR

    • Single HLA A or B serologic mismatch with DRB1 identity OR

    • HLA A or B serologic identity with a single DRB1 mismatch

    Patients 36 to 55 years of age must have a hematopoietic stem cell donor that is one of the following:

    • HLA A and B and HLA DRB1 identical OR

    • Single HLA A or B serologic mismatch with DRB1 identity

    Patients receiving umbilical cord blood must have an unrelated donor with no more than two antigen HLA A, B, or DRB1 mismatches

    --Patient Characteristics--

    Performance status: Karnofsky 70-100% OR Age less than 16 years: Lansky 50-100%

    Life expectancy: Not severly limited by another disease

    Hepatic: SGOT less than 3 times normal Bilirubin less than 2.5 mg/dL

    Renal: Creatinine normal OR Creatinine clearance or glomerular filtration rate greater than 50% normal

    Cardiovascular: If symptomatic, ventricular ejection fraction must be greater than 40% and must improve with exercise OR Shortening fraction normal on echocardiogram

    Pulmonary:
    • If symptomatic, DLCO greater than 45% predicted (corrected for hemoglobin)

    • In children unable to perform pulmonary function testing, oxygen saturation must be greater than 95%

    Other: HIV negative No significant active infections

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fairview University Medical Center Minneapolis Minnesota United States 55455

    Sponsors and Collaborators

    • Fairview University Medical Center

    Investigators

    • Study Chair: K. Scott Baker, Fairview University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00006056
    Other Study ID Numbers:
    • 199/15106
    • UMN-MT-1997-08
    • UMN-MT-9708
    First Posted:
    Jul 6, 2000
    Last Update Posted:
    Jun 24, 2005
    Last Verified:
    Oct 1, 2003

    Study Results

    No Results Posted as of Jun 24, 2005