Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure
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ClinicalTrials.gov Identifier: NCT03500731 |
Recruitment Status :
Recruiting
First Posted : April 18, 2018
Last Update Posted : February 11, 2022
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Condition or disease | Intervention/treatment | Phase |
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Idiopathic Pulmonary Fibrosis Emphysema or COPD | Biological: CD3/CD19 negative hematopoietic stem cells Drug: Rituximab Drug: Alemtuzumab Drug: Fludarabine Drug: Thiotepa Drug: G-CSF Drug: Hydroxyurea | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 8 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Lung Transplant in Tandem With Bone Marrow Transplant for Combined Lung and Bone Marrow Failure |
Actual Study Start Date : | April 19, 2018 |
Estimated Primary Completion Date : | December 2023 |
Estimated Study Completion Date : | December 2026 |

Arm | Intervention/treatment |
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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 Name: Rituxan Drug: Alemtuzumab Transplantation Conditioning
Other Name: Campath-1H Drug: Fludarabine Transplantation Conditioning
Other Name: Fludara, Oforta Drug: Thiotepa Transplantation Conditioning Drug: G-CSF Transplantation conditioning
Other Name: Neupogen, Granix, Zarxio, Filgrastim Drug: Hydroxyurea Transplantation Conditioning |
- Death [ Time Frame: Up to 2 years post stem cell transplant ]How many, if any, patients die
- Engraftment failure [ Time Frame: Up to 2 years post stem cell transplant ]How many, if any, develop engraftment failure
- Non-hematologic events [ Time Frame: Up to 2 years post stem cell transplant ]Any Grade 4 event that happens at any time points
- Hematological events [ Time Frame: after 30 days post stem cell transplant ]Any Grade 4 hematological events
- BOS Score [ Time Frame: at 1 year post lung transplant ]Bronchiolitis Obliterans Syndrome (BOS) score based off patient pulmonary function testing. Graded on scale (BOS0 to BOS3), BOS0 having a better outcome then BOS3
- T-cell Chimerism [ Time Frame: at 12 months post stem cell transplant ]The number of patients who have ≥25% donor T-cell chimerism
- Myeloid chimerism [ Time Frame: at 12 months post stem cell transplant ]The number of patients with myeloid disorders who attain ≥ 10% myeloid chimerism
- Restoration of blood cell count (in absence of growth factors) [ Time Frame: at 12 months post stem cell transplant ]Absolute neutrophil count (ANC)≥1000 per microliter of blood, platelets ≥50000 per microliter of blood and hematocrit ≥8 grams per deciliter of blood
- Feasibility of patients able to proceed to BMT within 6 months following lung transplantation [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who are able to proceed to BMT within 6 months following lung transplantation
- Independence [ Time Frame: up to 2 years post stem cell transplant ]The number of patients who are able to be independent from transfusions and growth factors for at least 7 days
- Independence [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who are able to be independent from transfusions and growth factors for at least 1 month
- Tolerance development to both host and pulmonary grafting [ Time Frame: Up to 2 years post stem cell transplant ]Development of tolerance to both the host and pulmonary graft
- Long-term complications [ Time Frame: Up to 2 years post stem cell transplant ]Long-term complications of combined solid organ and BMT
- Acute cellular rejection [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who develop acute cellular rejection
- Acute graft-versus-host-disease (GVHD) [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who develop acute graft-versus-host-disease (GVHD)
- Chronic graft-versus-host-disease (GVHD) [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who develop chronic graft-versus-host-disease (GVHD)
- Ability to withdrawal immunosuppression [ Time Frame: By 1 year post stem cell transplant ]The number of patients who are able to start immunosuppression withdrawal.
- Time to withdraw immunosuppression [ Time Frame: Up to 2 years post stem cell transplant ]Time from BMT to withdrawal of immunosuppression
- Prophylactic antimicrobial drugs [ Time Frame: Up to 2 years post stem cell transplant ]Time from BMT to independence for prophylactic antimicrobial drugs
- Treatment antimicrobial drugs [ Time Frame: up to 2 years post stem cell transplant ]Time from BMT to independence from treatment antimicrobial drugs
- Chronic lung allograft dysfunction [ Time Frame: 1 year post lung transplant ]The number of patients who develop chronic lung allograft dysfunction post lung transplant for all subjects, lung only and lung +stem cell transplant.
- Pace of immune reconstitution [ Time Frame: Up to 2 years post stem cell transplant ]The pace of immune reconstitution, systemically and in mucosal surfaces
- Mixed chimerism [ Time Frame: at Months 1, 3, 6 and 12 post stem cell transplant ]The number of patients who have the incidence of mixed chimerism (.5% host cells)
- In vitro immune tolerance [ Time Frame: Up to 2 years post stem cell transplant ]The number of patients who have in vitro immune tolerance

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Individuals must meet all of the following criteria in order to be eligible for this study.
- Subject must be able to understand and provide informed consent.
- Male or female, 18 through 60 years old, inclusive, at the time of informed consent.
- Meet criteria for UNOS listing for lung transplantation.
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Patients must have evidence of end stage lung disease. Examples of such diseases include but are not limited to:
- Pulmonary Fibrosis
- COPD/Emphysema
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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
- GFR ≥45 mL/min/1.73 m2.
- AST, ALT ≤4x upper limit of normal, total bilirubin ≤ 2.5 mg/dL, normal INR, albumin >3.0 g/dL
- Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%.
- Negative pregnancy test for females, unless surgically sterilized.
- 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.
- 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.
- 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 BMT.
- 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.
- 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 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.
- Uncontrolled infection, as determined by the appropriate imaging and/or 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500731
Contact: Paul Szabolcs, M.D. | 412-692-5427 | Paul.Szabolcs@chp.edu | |
Contact: Shawna H McIntyre, RN | 412-692-5552 ext 4126925552 | mcintyresm@upmc.edu |
United States, Pennsylvania | |
UPMC Presbyterian | Recruiting |
Pittsburgh, Pennsylvania, United States, 15214 | |
Contact: John McDyer, MD 412-648-6161 mcdyerjf@upmc.edu | |
Children's Hospital of Pittsburgh of UPMC | Recruiting |
Pittsburgh, Pennsylvania, United States, 15224 | |
Contact: Shawna H McIntyre, RN 412-692-5552 mcintyresm@upmc.edu | |
Principal Investigator: Paul Szabolcs, MD |
Responsible Party: | Paul Szabolcs, Chief, Division of Blood and Marrow Transplantation and Cellular Therapy, University of Pittsburgh |
ClinicalTrials.gov Identifier: | NCT03500731 |
Other Study ID Numbers: |
PRO17110400 |
First Posted: | April 18, 2018 Key Record Dates |
Last Update Posted: | February 11, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Pulmonary Emphysema Bone Marrow Failure Disorders Pancytopenia Fibrosis Emphysema Pathologic Processes Lung Diseases Respiratory Tract Diseases Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Bone Marrow Diseases Hematologic Diseases Rituximab |
Alemtuzumab Fludarabine Thiotepa Hydroxyurea Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists Antisickling Agents |