Trial record 1 of 4546 for:    Immunodeficiency
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Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders (MASCI)

This study has been terminated.
(slow accrual)
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
ClinicalTrials.gov Identifier:
NCT00579137
First received: December 19, 2007
Last updated: June 28, 2013
Last verified: June 2013
  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 (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.


Condition Intervention Phase
Severe Combined Immunodeficiency Disease
Severe Primary Immunodeficiency Disorder
Undefined T Cell Deficiency Disorder
Wiskott-Aldrick Syndrome
Biological: Campath -1H
Drug: Fludarabine
Biological: Anti-CD45
Procedure: Stem cell infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of Patients With Donor Engraftment [ Time Frame: 100 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patients Alive at 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
  • Number of Patients With Grade III or IV Toxicity [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Number of Patients With Grade III to IV Acute GVHD [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: October 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579137

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Investigators
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, Professor Pediatrics Hematology Oncology Center for Cell and Gene Therapy, 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
Results First Received: March 30, 2013
Last Updated: June 28, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Severe Combined Immunodeficiency Disease
Severe Primary Immunodeficiency Disorder
Undefined T cell Deficiency Disorder
Wiskott-Aldrick Syndrome
Allogeneic stem cell transplant
Fludarabine
monoclonal antibodies

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Antibodies, Monoclonal
Fludarabine monophosphate
Campath 1G
Fludarabine
Alemtuzumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014