Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders (MASCI)
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Purpose
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 and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them, YTH 24 and YTH 54 are rat IgG1 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-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 GvHD prophylaxis may be provided by administration of FK506.
| Condition | Intervention | Phase |
|---|---|---|
|
Immunologic Deficiency Syndrome |
Drug: Campath -1H Drug: Fludarabine Biological: Anti-CD45 Procedure: Stem cell infusion |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease And Other Primary Immunodeficiency Disorders |
- The combination of anti-CD45, anti-CD52 and fludarabine followed by transplantation of CD34+ selected cells promotes donor stem cell engraftment sufficient to • provide T cell function; • provide B cell function; • establish donor hematopoiesis [ Time Frame: 100 Days ] [ Designated as safety issue: Yes ]
- Survival of patients with SCID or PID undergoing this therapy. [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
- To investigate whether the combination of anti-CD45, anti-CD52 and fludarabine followed by transplantation of CD34+ selected cells can be performed with minimal and acceptable short term toxicity. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- To investigate the incidence of grade III - IV acute GVHD for patients with SCID following transplantation of CD34+ selected donor using MAb conditioning. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 21 |
| Study Start Date: | October 2007 |
| Study Completion Date: | June 2010 |
| Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
-
Drug: Campath -1H
Days -8,-7, and -6:
Intravenous:
Campath dose is weight based: for patients less than 15 kg administer Campath 3 mg; for patients >15 kg to 30 kg administer Campath 5 mg; for patients > 30 kg administer Campath 10 mg
Days -8,-7,-6,-5, and -4:
Intravenous 30 mg/m2
Days -5,-4,-3, and -2:
Intravenous, 400ug/kg over 6 hours
Show Detailed Description Eligibility| Ages Eligible for Study: | up to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
- HIV Seronegative
- Negative pregnancy test for females of childbearing age and willing to use an effective means of birth control.
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 Lansky/Karnofsky performance index score less than 70%
- Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation
Contacts and Locations| United States, Texas | |
| Texas Children's Hospital | |
| Houston, Texas, United States, 77030 | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Robert Krance, MD | Baylor College of Medicine |
| Study Chair: | Malcolm Brenner, MD | Baylor College of Medicine |
More Information
No publications provided
| Responsible Party: | Robert Krance, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00579137 History of Changes |
| Obsolete Identifiers: | NCT00609258 |
| Other Study ID Numbers: | 21123-MASCI |
| Study First Received: | December 19, 2007 |
| Last Updated: | December 21, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Baylor College of Medicine:
|
immunodeficiency disorders |
Additional relevant MeSH terms:
|
Immunologic Deficiency Syndromes Severe Combined Immunodeficiency Immune System Diseases Infant, Newborn, Diseases DNA Repair-Deficiency Disorders Metabolic Diseases Fludarabine Fludarabine monophosphate Alemtuzumab Campath 1G |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on October 17, 2012
