Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

NCT01852370 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: STUDY19090108
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

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)

Keywords

Lung transplantation; Bone Marrow Transplantation; Unrelated Donor; Cadaveric Donor; Deceased Donor; HLA-mismatch; BOLT; BMT; HSCT

Outcome Measures

Primary Outcomes (8)

• Safety: Death

  How many, if any, patients die.

  Up to 2 years post stem cell transplant

• Safety: Engraftment syndrome

  How many, if any, patients develop engraftment syndrome.

  Up to 2 years post stem cell transplant

• Safety: Engraftment failure

  How many patients, if any, develop engraftment failure.

  Up to 2 years post stem cell transplant

• Safety: Rituximab

  The number of grade 4 and 5 events potentially related to rituximab.

  Up to 2 years post stem cell transplant

• Efficacy: BOS score

  Bronchiolitis Obliterans Syndrome (BOS) score for all patients who receive both lungs and stem cell transplants.

  1 year post stem cell transplant

• Efficacy: T-cell chimerism

  The number of patients who have ≥ 25% donor T-cell chimerism.

  1 year post stem cell transplant

• Efficacy: Myeloid chimerism

  The number of patients with myeloid disorders (e.g. CGD) who attain ≥ 10% myeloid chimerism.

  1 year post stem cell transplant

• Efficacy: B-cell chimerism

  The number of patients with B-cell disorders who attain ≥ 10% B-cell chimerism.

  1 year post stem cell transplant

Secondary Outcomes (14)

• Feasibility of meeting BMT eligibility critieria

  Up to 2 years post stem cell transplant

• Tolerance

  Up to 2 years post stem cell transplant

• Long-term complications

  Up to 2 years post stem cell transplant

• Graft failure

  Up to 2 years post stem cell transplant

• Acute cellular rejection

  Up to 2 years post stem cell transplant

Study Arms (1)

BOLT+BMT

EXPERIMENTAL

All patients will receive a double lung transplant followed by a hematopoietic stem cell transplant. The lungs and stem cells are from the same partially HLA-matched cadaveric donor. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device.

Biological: CD3/CD19 negative allogeneic hematopoietic stem cells

Interventions

CD3/CD19 negative allogeneic hematopoietic stem cells BIOLOGICAL

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.

BOLT+BMT

Eligibility Criteria

• Age: 5 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject and/or parent guardian must be able to understand and provide informed consent.
• Male or female, 5 through 45 years old, inclusive, at the time of informed consent.
• Patients must have evidence of an underlying primary immunodeficiency for which BMT is clinically indicated.
• Examples of such diseases include, but are not limited to:
• Severe Combined Immunodeficiency
• Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
• Severe Chronic Neutropenia
• Chronic Granulomatous Disease
• Hyper IgE Syndrome or Job Syndrome
• CD40 or CD40L deficiency
• Wiskott-Aldrich Syndrome
• Mendelian Susceptibility to Mycobacterial Disease \[6\]
• GATA2 Associated Immunodeficiency NOTE: A genetic diagnosis is recommended, but not required.
• Patients must have evidence of end-stage lung disease and be candidates for bilateral orthotopic lung transplant as determined by the lung transplant team.
• GFR ≥ 50 mL/min/1.73 m2.

You may not qualify if:

• Individuals who meet any of these criteria are not eligible for this study:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• Patients who have underlying malignant conditions.
• Patients who have non-malignant conditions not requiring hematopoietic stem cell transplantation.
• HIV positive by serology or PCR, HTLV positive by serology.
• Females who are pregnant or who are lactating.
• Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell product.
• Uncontrolled systemic infection, as determined by the appropriate confirmatory testing e.g. blood cultures, PCR testing, etc.
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of transplant.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
• Eligibility Criteria to proceed to Bone Marrow Transplant
• GFR ≥ 50 mL/min/1.73 m2.
• AST, ALT ≤ 4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL.
• Cardiac ejection fraction ≥ 40% or shortening fraction of at least 26%.
• HIV negative by serology and PCR.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Neutropenia, severe chronic; Granulomatous Disease, Chronic; Job Syndrome; Wiskott-Aldrich Syndrome; Common Variable Immunodeficiency

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders

Study Officials

• Paul Szabolcs, MD

  Division of BMT and Cellular Therapy, Children's Hospital of Pittsburgh of UPMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplant, Children's Hospital of Pittsburgh of UPMC

Study Record Dates

• First Submitted: April 26, 2013
• First Posted: May 13, 2013
• Study Start: June 20, 2013
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)