NCT01852370

Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

Bilateral Orthotopic Lung Transplant in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant From Partially HLA-Matched Cadaveric Donors

• Status: Enrolling By Invitation
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Paul Szabolcs · Academic / Other
• Sex: All
• Age: 5 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.

Detailed description

This is an original IND for an investigator initiated phase I/II study. The primary purpose of the study is to evaluate the safety and efficacy of performing bilateral orthotopic lung transplantation (BOLT) followed by cadaveric, partially HLA-matched CD3+/CD19+-depleted hematopoietic stem cell transplantation (HSCT) from the same donor for patients with primary immunodeficiency diseases (PID) and end-stage lung disease. For many patients with primary immunodeficiencies, HSCT is a curative, life-saving therapy, resulting in restoration of function in the immune system. Patients with primary immunodeficiencies often develop pulmonary complications as a result of chronic or recurrent infections, making them ineligible for HSCT due to the high risk of mortality and pulmonary complications. Lung transplant prior to HSCT would allow for restoration of pulmonary function prior to HSCT, allowing PID patients to proceed to HSCT, which would be curative for the patient's underlying immunodeficiency. As a secondary aim after successful engraftment with donor bone marrow, there is realistic hope for tolerating planned withdrawal of immunosuppression achieving eventual freedom from all immunosuppressive drugs and attaining a tolerant state.

Conditions

• Severe Combined Immunodeficiency (SCID)
• Immunodeficiency With Predominant T-cell Defect, Unspecified
• Severe Chronic Neutropenia
• Chronic Granulomatous Disease (CGD)
• Hyper IgE Syndromes
• Hyper IgM Deficiencies
• Wiskott-Aldrich Syndrome
• Mendelian Susceptibility to Mycobacterial Disease
• Common Variable Immune Deficiency (CVID)

Interventions

Type	Name	Description
BIOLOGICAL	CD3/CD19 negative allogeneic hematopoietic stem cells	Negative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 36 hours of collection and given at time no less than 8 weeks post lung transplant.

Timeline

• Start date: 2013-06-20
• Primary completion: 2026-11-01
• Completion: 2027-11-01
• First posted: 2013-05-13
• Last updated: 2025-12-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study