Clinical trial NCT00004378: Stem Cell Transplantation (SCT) for Genetic Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thrombocytopenia
Metachromatic Leukodystrophy
Fanconi's Anemia
Thalassemia Major
Pure Red-Cell Aplasia
Inborn Errors of Metabolism
Keywords: Fanconi's anemia
amegakaryocytic thrombocytopenia
aplastic anemia
congenital pure red cell aplasia
genetic diseases and dysmorphic syndromes
hematologic disorders
inborn errors of metabolism
metachromatic leukodystrophy
pure red cell aplasia
rare disease
sphingolipidoses
thalassemia major
Lead sponsor: National Center for Research Resources (NCRR)
Sponsor class: NIH
Collaborators: name: University of California, Los Angeles
First posted: 1999-10-19
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: OBJECTIVES: I. Ascertain whether stem cell transplantation (SCT) is an effective method by which missing or dysfunctional enzymes can be replaced in patients with various inborn errors of metabolism.

II. Determine whether clinical manifestations of the specific disease may be arrested or reversed by this treatment.

Detailed description: PROTOCOL OUTLINE: Patients receive either cyclophosphamide and high dose total body irradiation (TBI) or busulfan and cyclophosphamide.

Cyclophosphamide IV is given on days -5 and -4 and TBI on days -2, -1, and 0. Busulfan is given orally every 6 hours on days -9 through -6 and cyclophosphamide IV on days -5 through -2. Patients rest on day -1.

Patients receive bone marrow infusion on day 0. For GVHD prophylaxis, patients receive methotrexate on day 1, then on days 3, 6, and 11. Cyclosporine IV begins on day -2 over 12 hours, followed by continuous infusion for 21 days. Then, oral doses of cyclosporine are given every 12 hours to patients who tolerate oral feeding. Cyclosporine is continued 6 months posttransplant, then tapered 10% per week and stopped.

Patients who receive genotypically HLA nonidentical stem cells undergo additional GVHD prophylaxis with methylprednisolone (IV or PO) or its equivalent every 12 hours on days 3 to day 100. Dose is then tapered as tolerated over 1 month.

Patients who receive cord blood stem cells receive methylprednisolone instead of methotrexate for GHVD prophylaxis. Methylprednisolone is given 3 times daily beginning on day 5 and continuing until day 17. Then, methylprednisolone is tapered 10% per week as clinically tolerated.

To accelerate engraftment, patients receive filgrastim IM daily beginning on day +1 and continuing until ANC equals 5000.

Eligibility criteria: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

* Hereditary enzymopathies, such as: Metachromatic leukodystrophy
* Congenital Immunodeficiencies
* Heritable hematologic disorders, such as: Thalassemia major Refractory Diamond-Blackfan anemia Fanconi anemia Amegakaryocytic thrombocytopenia

--Patient Characteristics--

* Age: Under 18
* Other: SCT is performed using a histocompatible related donor, an unrelated donor, or an unrelated cord blood donor Haploidentical donors are accepted for patients with severe congenital immunodeficiency

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Stephen A. Feig
role: STUDY_CHAIR
References: