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

This study is ongoing, but not recruiting participants.

Sponsored by: Fairview University Medical Center
Information provided by: Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier: NCT00006056
  Purpose

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.


Condition Intervention
Chediak-Higashi Syndrome
Graft Versus Host Disease
X-Linked Lymphoproliferative Syndrome
Familial Erythrophagocytic Lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis
Virus-Associated Hemophagocytic Syndrome
Drug: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: etoposide
Drug: filgrastim
Drug: methotrexate
Procedure: allogeneic hematopoietic stem cell transplantation

Genetics Home Reference related topics:   Chediak-Higashi syndrome   

ChemIDplus related topics:   Cyclophosphamide    Filgrastim    Etoposide    Methotrexate    Cyclosporine    Cyclosporin    Etoposide phosphate    Busulfan   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:   40
Study Start Date:   March 2000

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.

  Eligibility
Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006056

Locations
United States, Minnesota
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    
  More Information


Study ID Numbers:   199/15106, UMN-MT-1997-08, UMN-MT-9708
First Received:   July 5, 2000
Last Updated:   June 23, 2005
ClinicalTrials.gov Identifier:   NCT00006056
Health Authority:   Unspecified

Keywords provided by Office of Rare Diseases (ORD):
Chediak-Higashi syndrome  
X-linked lymphoproliferative syndrome  
disease-related problem/condition  
familial erythrophagocytic lymphohistiocytosis  
genetic diseases and dysmorphic syndromes  
graft versus host disease  
hematologic disorders  
hemophagocytic lymphohistiocytosis
histiocytosis
immunologic disorders and infectious disorders
primary immunodeficiency disease
rare disease
virus-associated hemophagocytic syndrome

Study placed in the following topic categories:
Cyclosporine
Clotrimazole
Graft versus host disease
Virus associated hemophagocytic syndrome
Miconazole
Leukocyte Disorders
Cyclophosphamide
Cyclosporins
Etoposide phosphate
Histiocytosis
Methotrexate
Chediak-Higashi syndrome
Chediak-Higashi Syndrome
Etoposide
Hemophagocytic lymphohistiocytosis
T cell immunodeficiency primary
Immunoproliferative Disorders
Lymphohistiocytosis, Hemophagocytic
Hematologic Diseases
Tioconazole
Rare Diseases
X-linked lymphoproliferative syndrome
Immunologic Deficiency Syndromes
Homologous wasting disease
Folic Acid
Antilymphocyte Serum
Virus Diseases
Lymphatic Diseases
Busulfan
Graft vs Host Disease

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Antifungal Agents
Abortifacient Agents
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Phagocyte Bactericidal Dysfunction
Disease
Reticuloendotheliosis
Immune System Diseases
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Histiocytosis, Non-Langerhans-Cell

ClinicalTrials.gov processed this record on October 06, 2008




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