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Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders (MASCI)

Primary Purpose

Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T Cell Deficiency Disorder

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Campath -1H
Fludarabine
Anti-CD45
Stem cell infusion
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Combined Immunodeficiency Disease focused on measuring Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T cell Deficiency Disorder, Wiskott-Aldrick Syndrome, Allogeneic stem cell transplant, Fludarabine, monoclonal antibodies

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Texas Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants With SCID or Primary Immunodeficiency Disorder

Arm Description

all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45

Outcomes

Primary Outcome Measures

Number of Patients With Donor Engraftment

Secondary Outcome Measures

Patients Alive at 1 Year
Number of Patients With Grade III or IV Toxicity
Number of Patients With Grade III to IV Acute GVHD

Full Information

First Posted
December 19, 2007
Last Updated
June 28, 2013
Sponsor
Baylor College of Medicine
Collaborators
Center for Cell and Gene Therapy, Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00579137
Brief Title
Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
Acronym
MASCI
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
October 2007 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
Center for Cell and Gene Therapy, Baylor College of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T Cell Deficiency Disorder, Wiskott-Aldrick Syndrome
Keywords
Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T cell Deficiency Disorder, Wiskott-Aldrick Syndrome, Allogeneic stem cell transplant, Fludarabine, monoclonal antibodies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Participants With SCID or Primary Immunodeficiency Disorder
Arm Type
Experimental
Arm Description
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
Intervention Type
Biological
Intervention Name(s)
Campath -1H
Other Intervention Name(s)
Alemtuzumab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Given intravenous on Days -8,-7,-6,-5, and -4 Dose is 30 mg/m2
Intervention Type
Biological
Intervention Name(s)
Anti-CD45
Intervention Description
Given intravenous over 6 hours on Days -5,-4,-3, and -2 Dose is 400 microgram/kg
Intervention Type
Procedure
Intervention Name(s)
Stem cell infusion
Intervention Description
stem cells are infused on day 0
Primary Outcome Measure Information:
Title
Number of Patients With Donor Engraftment
Time Frame
100 Days
Secondary Outcome Measure Information:
Title
Patients Alive at 1 Year
Time Frame
1 Year
Title
Number of Patients With Grade III or IV Toxicity
Time Frame
100 days
Title
Number of Patients With Grade III to IV Acute GVHD
Time Frame
100 days

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Krance, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Malcolm Brenner, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders

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