Clinical trial NCT00006054: Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Immunologic Deficiency Syndromes
Chediak-Higashi Syndrome
Common Variable Immunodeficiency
Graft Versus Host Disease
X-Linked Lymphoproliferative Syndrome
Familial Erythrophagocytic Lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis
X-linked Agammaglobulinemia
Wiskott-Aldrich Syndrome
Chronic Granulomatous Disease
X-linked Hyper IgM Syndrome
Severe Combined Immunodeficiency
Leukocyte Adhesion Deficiency Syndrome
Virus-Associated Hemophagocytic Syndrome
Keywords: Chediak-Higashi syndrome
Langerhans cell histiocytosis
Wiskott-Aldrich syndrome
X-linked agammaglobulinemia
X-linked hyper IgM syndrome
X-linked lymphoproliferative syndrome
chronic granulomatous disease
common variable immunodeficiency
complement deficiency
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
leukocyte adhesion deficiency syndrome
primary immunodeficiency disease
rare disease
severe combined immunodeficiency
virus-associated hemophagocytic syndrome
Lead sponsor: Office of Rare Diseases (ORD)
Sponsor class: NIH
First posted: 2000-07-06
Sex: ALL
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: OBJECTIVES: I. Provide curative immunoreconstituting allogeneic bone marrow transplantation for patients with primary immunodeficiencies.

II. Determine relevant outcomes of this treatment in these patients including quality of survival, extent of morbidity and mortality from complications of the treatment (e.g., graft versus host disease, regimen related toxicities, B- cell lymphoproliferative disease), and completeness of functional immunoreconstitution.

Detailed description: PROTOCOL OUTLINE: Patients with severe combined immunodeficiency (SCID) using a matched sibling donor receive allogeneic bone marrow or umbilical cord blood transplantation on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with SCID using donors other than histocompatible siblings, Wiskott Aldrich syndrome using a histocompatible sibling donor, Wiskott Aldrich syndrome and under 5 years of age using donors other than histocompatible siblings, X-linked CD40 ligand deficiency using a histocompatible sibling donor, X-linked CD40 ligand deficiency and under 5 years of age using donors other than histocompatible siblings, other primary immunodeficiencies without manifestations of hemophagocytosis using a histocompatible sibling donor, or other primary immunodeficiencies without manifestations of hemophagocytosis and under 5 years of age using donors other than histocompatible siblings receive busulfan IV over 2 hours every 6 hours on days -9 to -6, cyclophosphamide IV on days -5 to -2, and antithymocyte globulin (ATG) twice daily on days -4 to -1. Allogeneic bone marrow or umbilical cord blood transplantation takes place on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with hemophagocytic lymphohistiocytosis, Chediak Higashi syndrome, X-linked lymphoproliferative syndrome, severe progressive Langerhans cell histiocytosis, or other primary immunodeficiencies with complications of hemophagocytosis receive busulfan IV over 2 hours every 6 hours on days -9 to -6, cyclophosphamide IV over 2 hours on days -5 to -2, etoposide IV over 22 hours on days -5 to -3, and ATG IV twice daily on days -2, -1, 1, and 2. Allogeneic bone marrow or umbilical cord blood transplantation takes place on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with Wiskott Aldrich syndrome or other primary immunodeficiencies without manifestations of hemophagocytosis, who are over 5 years of age and using donors other than histocompatible siblings, receive busulfan IV over 2 hours every 6 hours on days -6 and -5, cyclophosphamide IV over 2 hours on days -4 and -3, total body irradiation on day -2, and ATG IV over 2 hours twice daily on days -2, -1, 2, and 3. Allogeneic bone marrow or umbilical cord blood transplantation takes place on days 0 and 1. Patients receive GVHD prophylaxis with methylprednisolone IV every 12 hours on days 2-21, oral prednisone every 12 hours on days 22-100 and then tapered off over days 101 to 128, and cyclosporine IV over 2 hours every 8-12 hours on days -3 to 100.

All patients are followed as determined by their primary physician.

Eligibility criteria: * Severe combined immunodeficiency All ages with histocompatible sibling donors or with other donors OR Wiskott Aldrich syndrome All ages with histocompatible sibling donors or with other donors OR X-linked CD40 ligand deficiency All ages with histocompatible sibling donors OR Under 5 years of age with donors other than histocompatible siblings OR Other primary immunodeficiencies without manifestations of hemophagocytosis All ages with histocompatible sibling donors or with other donors OR Hemophagocytic lymphohistiocytosis (HLH) Familial erythrophagocytic lymphohistiocytosis (FEL), familial HLH (FHLH), recurrent virus-associated hemophagocytic syndrome (VAHS) All ages with related or unrelated donors OR Chediak Higashi syndrome All ages with related or unrelated donors OR X-linked lymphoproliferative syndrome All ages with related or unrelated donors OR Other primary immunodeficiencies with complication of hemophagocytosis All ages with related or unrelated donors OR Severe progressive Langerhans cell histiocytosis All ages with related or unrelated donors

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Fairview University Medical Center
state: Minnesota
Study officials:
affiliation: Fairview University Medical Center
name: K. Scott Baker
role: STUDY_CHAIR
References: