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

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ClinicalTrials.gov Identifier: NCT00579137
Recruitment Status : Terminated (slow accrual)
First Posted : December 21, 2007
Results First Posted : July 2, 2013
Last Update Posted : July 2, 2013
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Information provided by (Responsible Party):
Robert Krance, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE December 19, 2007
First Posted Date  ICMJE December 21, 2007
Results First Submitted Date  ICMJE March 30, 2013
Results First Posted Date  ICMJE July 2, 2013
Last Update Posted Date July 2, 2013
Study Start Date  ICMJE October 2007
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2013)
Number of Patients With Donor Engraftment [ Time Frame: 100 Days ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2007)
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 ]
Change History Complete list of historical versions of study NCT00579137 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2013)
  • Patients Alive at 1 Year [ Time Frame: 1 Year ]
  • Number of Patients With Grade III or IV Toxicity [ Time Frame: 100 days ]
  • Number of Patients With Grade III to IV Acute GVHD [ Time Frame: 100 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2007)
Survival of patients with SCID or PID undergoing this therapy. [ Time Frame: 1 Year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Combined Immunodeficiency Disease
  • Severe Primary Immunodeficiency Disorder
  • Undefined T Cell Deficiency Disorder
  • Wiskott-Aldrick Syndrome
Intervention  ICMJE
  • Biological: Campath -1H

    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 Name: Alemtuzumab
  • Drug: Fludarabine

    Given intravenous on Days -8,-7,-6,-5, and -4

    Dose is 30 mg/m2

    Other Name: Fludara
  • Biological: Anti-CD45

    Given intravenous over 6 hours on Days -5,-4,-3, and -2

    Dose is 400 microgram/kg

  • Procedure: Stem cell infusion
    stem cells are infused on day 0
Study Arms  ICMJE 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
Interventions:
  • Biological: Campath -1H
  • Drug: Fludarabine
  • Biological: Anti-CD45
  • Procedure: Stem cell infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 28, 2013)
3
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2007)
21
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00579137
Other Study ID Numbers  ICMJE 21123-MASCI
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert Krance, Baylor College of Medicine
Study Sponsor  ICMJE Baylor College of Medicine
Collaborators  ICMJE
  • Center for Cell and Gene Therapy, Baylor College of Medicine
  • Texas Children's Hospital
Investigators  ICMJE
Principal Investigator: Robert Krance, MD Baylor College of Medicine
Study Chair: Malcolm Brenner, MD Baylor College of Medicine
PRS Account Baylor College of Medicine
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP