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

NCT00006056 | Unknown

• 3 other identifiers: 199/15106UMN-MT-1997-08UMN-MT-9708
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Chediak-Higashi Syndrome; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; Virus-Associated Hemophagocytic Syndrome

Keywords

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

Interventions

anti-thymocyte globulin DRUG

busulfan DRUG

cyclophosphamide DRUG

cyclosporine DRUG

etoposide DRUG

filgrastim DRUG

methotrexate DRUG

allogeneic hematopoietic stem cell transplantation PROCEDURE

Eligibility Criteria

• Age: 0 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fairview University Medical Center: lead

Study Sites (1)

Fairview University Medical Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Chediak-Higashi Syndrome; Graft vs Host Disease; Lymphoproliferative Disorders; Lymphohistiocytosis, Hemophagocytic; Genetic Diseases, Inborn; Hematologic Diseases; Histiocytosis; Immune System Diseases; Communicable Diseases; Primary Immunodeficiency Diseases; Rare Diseases

Interventions

Antilymphocyte Serum; Busulfan; Cyclophosphamide; Cyclosporine; Etoposide; Filgrastim; Methotrexate

Condition Hierarchy (Ancestors)

Albinism; Eye Diseases, Hereditary; Eye Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Lymphatic Diseases; Immunoproliferative Disorders; Histiocytosis, Non-Langerhans-Cell; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• K. Scott Baker

  Fairview University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 5, 2000
• First Posted: July 6, 2000
• Study Start: March 1, 2000
• Last Updated: June 24, 2005

Record last verified: 2003-10

Locations

US (1)