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