Clinical trial NCT03500731: Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure
Official title: Lung Transplant in Tandem with Bone Marrow Transplant for Combined Lung and Bone Marrow Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Emphysema or COPD
Keywords: Lung Transplantation
Stem Cell Transplantation
Idiopathic Pulmonary Fibrosis
Emphysema or COPD
Bone marrow transplantation
Cadaveric donor
Unrelated donor
HLA-Mismatch
BMT
HSCT
IPF
Pulmonary fibrosis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2018-04-18
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether a lung transplantation prior to bone marrow transplantation (BMT) would allow for restoration of pulmonary function prior to BMT, allowing to proceed to BMT, to restore hematologic function.

Detailed description: The primary purpose of the study is to evaluate the safety and efficacy of performing lung transplantation followed by cadaveric, partially HLA-matched (≥1/6 HLA-match with an identical ABO blood type) CD3+/CD19+ depleted bone marrow transplantation in bone marrow failure and end-stage lung disease. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease for which lung transplantation is the only therapy shown to prolong survival. Given the association of IPF with hematologic cytopenias and bone marrow failure, it is proposed that a tandem lung transplantation and bone marrow transplantation from a single cadaveric donor could be successful. This protocol focuses on performing combined transplantation for candidates that are unable to undergo standard lung transplantation. Lung transplantation prior to bone marrow transplantation (BMT) would allow for restoration of pulmonary function prior to BMT, and to restore hematologic function post BMT transplantation. The secondary objectives are to evaluate the feasibility and long-term complications associated with combined solid organ and BMT including the ability to initiate and successfully withdraw from immunosuppression following BMT and to attain independence from growth factors, red blood cell or platelet transfusions.

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.

Primary outcomes:
measure: Death
timeFrame: Up to 2 years post stem cell transplant
measure: Engraftment failure
timeFrame: Up to 2 years post stem cell transplant
measure: Non-hematologic events
timeFrame: Up to 2 years post stem cell transplant
measure: Hematological events
timeFrame: after 30 days post stem cell transplant
measure: BOS Score
timeFrame: at 1 year post lung transplant
measure: T-cell Chimerism
timeFrame: at 12 months post stem cell transplant
measure: Myeloid chimerism
timeFrame: at 12 months post stem cell transplant
measure: Restoration of blood cell count (in absence of growth factors)
timeFrame: at 12 months post stem cell transplant
Secondary outcomes:
measure: Feasibility of patients able to proceed to BMT within 6 months following lung transplantation
timeFrame: Up to 2 years post stem cell transplant
measure: Independence
timeFrame: up to 2 years post stem cell transplant
measure: Independence
timeFrame: Up to 2 years post stem cell transplant
measure: Tolerance development to both host and pulmonary grafting
timeFrame: Up to 2 years post stem cell transplant
measure: Long-term complications
timeFrame: Up to 2 years post stem cell transplant
measure: Acute cellular rejection
timeFrame: Up to 2 years post stem cell transplant
measure: Acute graft-versus-host-disease (GVHD)
timeFrame: Up to 2 years post stem cell transplant
measure: Chronic graft-versus-host-disease (GVHD)
timeFrame: Up to 2 years post stem cell transplant
measure: Ability to withdrawal immunosuppression
timeFrame: By 1 year post stem cell transplant
measure: Time to withdraw immunosuppression
timeFrame: Up to 2 years post stem cell transplant
measure: Prophylactic antimicrobial drugs
timeFrame: Up to 2 years post stem cell transplant
measure: Treatment antimicrobial drugs
timeFrame: up to 2 years post stem cell transplant
measure: Chronic lung allograft dysfunction
timeFrame: 1 year post lung transplant
Other outcomes:
measure: Pace of immune reconstitution
timeFrame: Up to 2 years post stem cell transplant
measure: Mixed chimerism
timeFrame: at Months 1, 3, 6 and 12 post stem cell transplant
measure: In vitro immune tolerance
timeFrame: Up to 2 years post stem cell transplant
Locations:
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
References: