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

Brief Title

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


Brief Summary

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

      II. 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 Type

Interventional




Condition

Chediak-Higashi Syndrome

Intervention

anti-thymocyte globulin


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

40

Start Date

March 2000



Eligibility Criteria

        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
      

Gender

All

Ages

N/A - 55 Years

Accepts Healthy Volunteers

No

Contacts

K. Scott Baker, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00006056

Organization ID

199/15106

Secondary IDs

UMN-MT-1997-08


Study Sponsor

Fairview University Medical Center


Study Sponsor

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


Verification Date

October 2003