Lung and bone marrow transplantation for patients with lung and bone marrow failure

Lung Transplant in Tandem With Bone Marrow Transplant for Combined Lung and Bone Marrow Failure

This study tests if doing a lung transplant followed by a bone marrow transplant can help people with severe lung disease and bone marrow failure feel better and live longer.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: University of Pittsburgh (other)
• Locations: 2 sites (Pittsburgh, Pennsylvania and 1 other locations)
• Trial ID: NCT03500731 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of performing lung transplantation followed by bone marrow transplantation in patients with end-stage lung disease and bone marrow failure. It focuses on individuals with idiopathic pulmonary fibrosis or COPD who are unable to undergo standard lung transplantation. The approach involves using a single cadaveric donor for both transplants, with the goal of restoring pulmonary function before the bone marrow transplant. The study will also assess long-term complications and the feasibility of immunosuppression withdrawal post-transplant.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 60 with end-stage lung disease and evidence of bone marrow failure.

Not a fit: Patients with conditions that do not involve end-stage lung disease or bone marrow failure may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival and quality of life for patients with severe lung and bone marrow conditions.

How similar studies have performed: While combined lung and bone marrow transplantation is a novel approach, similar studies have shown promise in addressing complex cases of organ failure.

Eligibility criteria

Inclusion Criteria:

Individuals must meet all of the following criteria in order to be eligible for this study.

1. Subject must be able to understand and provide informed consent.
2. Male or female, 18 through 60 years old, inclusive, at the time of informed consent.
3. Meet criteria for UNOS listing for lung transplantation.
4. Patients must have evidence of end stage lung disease. Examples of such diseases include but are not limited to:

   * Pulmonary Fibrosis
   * COPD/Emphysema
5. Patients must have evidence of bone marrow failure with abnormal low cell count in at least one hematopoietic line, making the patient a poor candidate for long-term immunosuppressive therapy. Eligible patients must meet at least one of the following criteria:

   * Unexplained, non-drug induced neutropenia with absolute neutrophils counts of \<1500/µL the previous year, confirmed by repeat testing
   * Unexplained, non-drug induced thrombocytopenia with mean platelets counts of \<100,000/µL the previous year, confirmed by repeat testing
   * Unexplained, non-hemolytic anemia, with a hemoglobin level of \< 12 g/dL the previous year, confirmed by repeat testing
6. GFR ≥45 mL/min/1.73 m2.
7. AST, ALT ≤4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL, normal INR, albumin \>3.0 g/dL
8. Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%.
9. Negative pregnancy test for females, unless surgically sterilized.
10. All females of childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause birth defect.
11. Subject will also be counseled regarding the potential risks of infertility following BMT and advised to discuss sperm banking or oocyte harvesting.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for this study.

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
2. Patients who have underlying malignant conditions.
3. Patients who have non-malignant conditions not requiring BMT.
4. HIV positive by serology or PCR, HTLV positive by serology. If HTLV serology is positive, it will be confirmed by nucleic acid testing (NAT). If HTLV NAT is negative, subject will remain eligible regardless of HTLV serology result.
5. Females who are pregnant or who are lactating.
6. Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell product.
7. Uncontrolled pulmonary infection, as determined by radiographic findings and/or significant clinical deterioration. NOTE: Pulmonary colonization with multiple organisms is common and will not be considered an exclusion criterion.
8. Uncontrolled infection, as determined by the appropriate imaging and/or confirmatory testing e.g. blood cultures, PCR testing, etc.
9. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of transplant.
10. 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.

Where this trial is running

Pittsburgh, Pennsylvania and 1 other locations

• UPMC Presbyterian — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Paul Szabolcs, M.D.

Conditions: Idiopathic Pulmonary Fibrosis, Emphysema or COPD, Lung Transplantation, Stem Cell Transplantation, Bone marrow transplantation, Cadaveric donor, Unrelated donor, HLA-Mismatch