Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders

NCT00579137 | Terminated Phase 1 Results DMC

• 1 other identifier: 21123-MASCI
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Donor Engraftment

  100 Days

Secondary Outcomes (3)

• Patients Alive at 1 Year

  1 Year

• Number of Patients With Grade III or IV Toxicity

  100 days

• Number of Patients With Grade III to IV Acute GVHD

  100 days

Study Arms (1)

Participants With SCID or Primary Immunodeficiency Disorder

EXPERIMENTAL

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

Biological: Campath -1H; Drug: Fludarabine; Biological: Anti-CD45; Procedure: Stem cell infusion

Interventions

Campath -1H BIOLOGICAL

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

Also known as: Alemtuzumab

Participants With SCID or Primary Immunodeficiency Disorder

Fludarabine DRUG

Given intravenous on Days -8,-7,-6,-5, and -4 Dose is 30 mg/m2

Also known as: Fludara

Participants With SCID or Primary Immunodeficiency Disorder

Anti-CD45 BIOLOGICAL

Given intravenous over 6 hours on Days -5,-4,-3, and -2 Dose is 400 microgram/kg

Participants With SCID or Primary Immunodeficiency Disorder

Stem cell infusion PROCEDURE

stem cells are infused on day 0

Participants With SCID or Primary Immunodeficiency Disorder

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.
• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases; Primary Immunodeficiency Diseases

Interventions

Alemtuzumab; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Robert Krance, MD
• Organization: Baylor

rkrance@bcm.edu

832-824-4661

Study Officials

• Robert Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Malcolm Brenner, MD

  Baylor College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Pediatrics Hematology Oncology Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 2, 2013
• Results First Posted: July 2, 2013

Record last verified: 2013-06

Locations

US (1)