Severe Combined Immunodeficiency Disease Clinical Trial
— MASCIOfficial title:
CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease (SCID) And Other Primary Immunodeficiency Disorders
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched (up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them are rat IgG1 (immunoglobulin G1) antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. Campath 1H, Alemtuzumab, has been licensed to treat B-cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with SCID, in whom the use of conventional chemotherapeutic agents for conditioning may produce or aggravate unacceptable and even lethal short term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial GvHD prophylaxis. Additional Graft versus Host Disease (GvHD) prophylaxis may be provided by administration of FK506.
| Status | Terminated |
| Enrollment | 3 |
| Est. completion date | October 2009 |
| Est. primary completion date | October 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A and older |
| Eligibility |
Inclusion Criteria: - Patients with a diagnosis of: Severe combined immunodeficiency disease This includes patients whose SCID is characterized by gene specific mutations as well as patients with clinically severe combined immunodeficiency without a defined genetic cause in which the diagnosis will be determined by a combination of clinical course with lymphocyte quantification and function assays. OR Severe primary immunodeficiency disorder, including undefined T cell deficiency disorder, Wiskott-Aldrich syndrome, and other severe immunodeficiencies for which satisfactory conventional therapy does not exist. - Availability of an HLA mismatched (up to one haplotype) family member or an HLA matched or mismatched (up to one antigen) unrelated donor. - Creatinine < 2.5 x normal for age. - Life expectancy greater than 6 weeks - Lansky/Karnofsky greater than or equal to 70% Exclusion Criteria: - Patients with an HLA matched related donor - Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%) - Patients with known allergy to rat serum products - Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation - HIV positive - Pregnant |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Texas Children's Hospital | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Patients With Donor Engraftment | 100 Days | No | |
| Secondary | Patients Alive at 1 Year | 1 Year | Yes | |
| Secondary | Number of Patients With Grade III or IV Toxicity | 100 days | Yes | |
| Secondary | Number of Patients With Grade III to IV Acute GVHD | 100 days | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT04172181 -
Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
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