- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00579137
Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders (MASCI)
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Donor Stem Cell Processing for Mismatched Donors: Harvested peripheral blood stem cells will be enriched for CD34 cells using the CliniMACS CD34 Reagent system, according to Center for Cell and Gene Therapy (CAGT) SOPs.
Stem Cell Transplant Conditioning
Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered i.v. q4h during the period of the course of the Campath and Anti-CD45 infusions.
Day
8 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
7 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
6 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
5 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
4 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
3 YTH 24/54 400ug/kg over 6 hr
2 YTH 24/54 400ug/kg over 6 hr
1 rest
0 Stem Cell Infusion
Campath 1H Infusion- Campath dose is weight based: for patients less than 15 killograms (kg) administer Campath 3 mg; for patients >15 kg to 30 kg administer Campath 5 mg; for patients > 30 kg administer Campath 10 mg. Campath will be dosed and administered as per CAGT SOP.
Anti-CD45- Infusion Anti-CD45 infusion will be administered according to CAGT SOPs. 3 ml of heparinized blood will be drawn 48 hr post Anti-CD45 to evaluate for free Anti-CD45 levels in the plasma. This estimation will be used to determine whether treatment with irradiated leukocytes is required before the bone marrow is infused.
GVHD Prophylaxis- GVHD prophylaxis will be achieved through positive selection for CD34 resulting in > 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GVHD after haploidentical transplants if recipients receive stem cell populations containing <5 x 10 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo. Patients who develop acute or chronic GVHD will be managed according to CAGT SOPs.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Texas Children's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Participants With SCID or Primary Immunodeficiency Disorder
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
|
Given intravenous on Days -8,-7, and -6 Campath dose is weight based: for patients less than 15 kg the dose is 3 mg; for patients >15 kg to 30 kg the dose 5 mg; for patients > 30 kg the dose is 10 mg
Other Names:
Given intravenous on Days -8,-7,-6,-5, and -4 Dose is 30 mg/m2
Other Names:
Given intravenous over 6 hours on Days -5,-4,-3, and -2 Dose is 400 microgram/kg
stem cells are infused on day 0
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Patients With Donor Engraftment
Time Frame: 100 Days
|
100 Days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Patients Alive at 1 Year
Time Frame: 1 Year
|
1 Year
|
Number of Patients With Grade III or IV Toxicity
Time Frame: 100 days
|
100 days
|
Number of Patients With Grade III to IV Acute GVHD
Time Frame: 100 days
|
100 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Malcolm Brenner, MD, Baylor College of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Immune System Diseases
- Infant, Newborn, Diseases
- Genetic Diseases, Inborn
- DNA Repair-Deficiency Disorders
- Disease
- Immunologic Deficiency Syndromes
- Primary Immunodeficiency Diseases
- Severe Combined Immunodeficiency
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Fludarabine
- Alemtuzumab
Other Study ID Numbers
- 21123-MASCI
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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