Bilateral Orthotopic Lung Transplant - Bone Marrow Transplant

NCT03330795 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: DAIT BOLT-BMTDAIT RTB-003U01AI125050NIAID DAIT CRMS ID#: 32935
• Study Type: interventional
• Target: 5
• 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 CD3+/CD19+ depleted bone marrow transplant (BMT) is safe and effective for individuals aged 10 through 45 years with the diagnosis of primary immunodeficiency (PID) and end-stage lung disease. The enrollment goal: 8 participants who receive both BOLT and BMT.

Conditions

Primary Immunodeficiency; PID

Keywords

end-stage lung disease; Bilateral Orthotopic Lung Transplant (BOLT) candidate; CD3/CD19 negative allogeneic hematopoietic stem cells (HSCT); CD3+/CD19+ depleted Bone Marrow Transplant (BMT); Cadaveric (Deceased) Donor; Unrelated (Deceased) Donor

Outcome Measures

Primary Outcomes (9)

• Safety: Death

  How many, if any, participants die during study participation.

  Average of approximately 31 months for those who received an initial transplant

• Safety: Engraftment Syndrome

  How many, if any, participants develop engraftment syndrome.

  Average of ~7.5 months of time post BMT for those receiving both lung and BMT transplants.

• Engraftment Failure

  Average of ~7.5 months of time post BMT for those receiving both lung and BMT transplants.

• Grade 4 or 5 Events Potentially Attributable to Rituximab

  Average of ~25 months.

• BOS at 1 Year Post BOLT

  Diagnosis of BOS (Bronchiolitis Obliterans Syndrome) at any time up to 1 year post BOLT. BOS is one of the undesirable complications of lung transplantation.

  throughout the first year post BOLT

• Efficacy: Count of Participants With Requirement for Supplemental Oxygen and/or Ventilatory Support

  The number of participant(s) who need either supplemental oxygen and/or ventilator support (noninvasive/invasive) will be assessed using the Bronchiolitis Obliterans Syndrome (BOS) Classification Score for pulmonary function (e.g., the Forced Expiratory Volume in 1 Second (FEV1). FEV1 is air volume exhaled in 1 second during spirometry, a lung function test. (Continuing dependence on supplemental oxygen or ventilatory support is an undesirable outcome of lung transplantation).

  at 1 Year Post Lung Transplant (BOLT)

• Efficacy: Count of Participants With T-cell Chimerism

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

  1 Year Post Bone Marrow Transplant (BMT)

• Efficacy: Count of Participants With Myeloid Chimerism

  The number of participants with myeloid disorders (e.g. Chronic Granulomatous Disease \[CGD\]) who attain ≥ 10% myeloid chimerism.

  1 Year Post Bone Marrow Transplant (BMT)

• Efficacy: Count of Participants B-cell Chimerism

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

  1 Year Post Bone Marrow Transplant (BMT)

Secondary Outcomes (12)

• Count of Participants Able to Proceed to BMT

  6 Months Post Lung Transplant (BOLT)

• Count of Participants Who Achieve Tolerance

  Average of ~7.5 months of time post BMT for those receiving both lung and BMT transplants.

• Long Term Complications of Combined Solid Organ and Bone Marrow Transplant

  Average of ~7.5 months of time post BMT for those receiving both lung and BMT transplants.

• Count of Participants Who Develop Acute Cellular Rejection and Graft Failure

  Average of ~7.5 months of time post BMT for those receiving both lung and BMT transplants.

• Count of Participants Able to Initiate Withdrawal of Immunosuppression

  1 year following BMT

Study Arms (1)

CD3/CD19 neg allogeneic BMT

EXPERIMENTAL

Participants may receive a double lung transplant followed by a bone marrow (hematopoietic stem cells) transplant, if a partially HLA-matched organ offer is accepted. The lungs and allogeneic hematopoietic stem cells will be from the same partially HLA-matched cadaveric donor. Prior to marrow transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device.

Biological: CD3/CD19 neg allogeneic BMT

Interventions

CD3/CD19 neg allogeneic BMT BIOLOGICAL

Negative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 36 hours of collection, and cryopreserved for later marrow transplantation. BMT conditioning and transplantation will start at least 8 weeks or more post lung transplant - once the participant is clinically judged suitable to undergo BMT conditioning and transplantion.

Also known as: CD3+/CD19+ depleted HSCT

CD3/CD19 neg allogeneic BMT

Eligibility Criteria

• Age: 10 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;
• Subject fulfills criteria for United Network of Organ Sharing (UNOS) listing;
• Subject must have evidence of an underlying primary immunodeficiency for which Bone Marrow Transplant (BMT) is clinically indicated. Examples of such diseases include, but are not limited to:
• Severe Combined Immunodeficiency (SCID)
• Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
• Severe Chronic Neutropenia
• Chronic Granulomatous Disease (CGD)
• Hyper Immunoglobulin E (IgE) Syndrome or Job's Syndrome
• CD40 or CD40L deficiency
• Wiskott-Aldrich Syndrome
• Mendelian Susceptibility to Mycobacterial Disease
• GATA2-associated Immunodeficiency.
• Subjects must have evidence of end-stage lung disease and be candidates for bilateral orthotopic lung transplant as determined by the lung transplant team;
• Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2;
• Aspartate aminotransferase (AST), Alanine aminotransaminase (ALT) ≤ 4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL, normal INR;

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol;
• Subjects who have underlying malignant conditions;
• Subjects who have non-malignant conditions that do not require hematopoietic stem cell transplantation;
• Human Immunodeficiency Virus (HIV) positive by serology or polymerase chain reaction (PCR), human T-lymphotropic virus (HTLV) positive by serology;
• Females who are pregnant or who are lactating;
• Allergy to dimethyl sulfoxide (DMSO) or any other ingredient used in the manufacturing of the stem cell product;
• Uncontrolled pulmonary infection, as determined by radiographic findings and/or significant clinical deterioration.
• 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; or
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• University of Pittsburgh: collaborator
• PPD Development, LP: collaborator

Study Sites (1)

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Death

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

240-669-5064

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: December 1, 2017
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: July 22, 2025
• Results First Posted: July 22, 2025

Record last verified: 2025-07

Locations

US (1)