Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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. HIV positive by serology or PCR, HTLV positive by serology.

4. Females who are pregnant or who are lactating.

5. Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell product.

6. Uncontrolled infection, as determined by the appropriate imaging and/or confirmatory testing e.g. blood cultures, PCR testing, etc.

7. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of transplant.

8. 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Lung and Bone Marrow Transplantation
All patients will undergo a cadaveric, partially HLA-matched lung transplantation followed by a CD3+/CD19+ depleted BMT from the same donor. In this study, the investigators will use a ≥1/6 HLA-matched T cell depleted bone marrow transplantation from a cadaveric organ donor with an identical ABO blood type as the recipient. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device. Subjects will undergo lung transplantation utilizing standard induction regimens selected by the CO-PIs based on the subject's underlying comorbidities and allosensitization. Rituximab may be initiated prior to the lung transplantation with tacrolimus as the ongoing maintenance immunosuppression. Subjects will undergo BMT utilizing CD3+/CD19+-depleted bone marrow with bone marrow conditioning beginning no less than 8 weeks after lung transplantation. Bone marrow will be recovered alongside solid organs and will be processed and cryopreserved.
  • Biological: CD3/CD19 negative hematopoietic stem cells
    Negative selection for CD3/CD19 will be performed on CliniMACS® depletion device and given at time no less than 8 weeks post lung transplantation
  • Drug: Rituximab
    Transplantation Conditioning
    Other names:
    • Rituxan
  • Drug: Alemtuzumab
    Transplantation Conditioning
    Other names:
    • Campath-1H
  • Drug: Fludarabine
    Transplantation Conditioning
    Other names:
    • Fludara, Oforta
  • Drug: Thiotepa
    Transplantation Conditioning
  • Drug: G-CSF
    Transplantation conditioning
    Other names:
    • Neupogen, Granix, Zarxio, Filgrastim
  • Drug: Hydroxyurea
    Transplantation Conditioning

Recruiting Locations

Trials Today and nearby locations

Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
Contact:
Shawna H McIntyre, RN
412-692-5552
mcintyresm@upmc.edu

UPMC Presbyterian
Pittsburgh, Pennsylvania 15214
Contact:
John McDyer, MD
412-648-6161
mcdyerjf@upmc.edu

More Details

NCT ID
NCT03500731
Status
Recruiting
Sponsor
Paul Szabolcs

Study Contact

Paul Szabolcs, M.D.
412-692-5427
Paul.Szabolcs@chp.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.