Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure

NCT03500731 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY19110120
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (8)

• Death

  How many, if any, patients die

  Up to 2 years post stem cell transplant

• Engraftment failure

  How many, if any, develop engraftment failure

  Up to 2 years post stem cell transplant

• Non-hematologic events

  Any Grade 4 event that happens at any time points

  Up to 2 years post stem cell transplant

• Hematological events

  Any Grade 4 hematological events

  after 30 days post stem cell transplant

• BOS Score

  Bronchiolitis Obliterans Syndrome (BOS) score based off patient pulmonary function testing. Graded on scale (BOS0 to BOS3), BOS0 having a better outcome then BOS3

  at 1 year post lung transplant

• T-cell Chimerism

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

  at 12 months post stem cell transplant

• Myeloid chimerism

  The number of patients with myeloid disorders who attain ≥ 10% myeloid chimerism

  at 12 months post stem cell transplant

• Restoration of blood cell count (in absence of growth factors)

  Absolute neutrophil count (ANC)≥1000 per microliter of blood, platelets ≥50000 per microliter of blood and hematocrit ≥8 grams per deciliter of blood

  at 12 months post stem cell transplant

Secondary Outcomes (13)

• Feasibility of patients able to proceed to BMT within 6 months following lung transplantation

  Up to 2 years post stem cell transplant

• Independence

  up to 2 years post stem cell transplant

• Independence

  Up to 2 years post stem cell transplant

• Tolerance development to both host and pulmonary grafting

  Up to 2 years post stem cell transplant

• Long-term complications

  Up to 2 years post stem cell transplant

Other Outcomes (3)

• Pace of immune reconstitution

  Up to 2 years post stem cell transplant

• Mixed chimerism

  at Months 1, 3, 6 and 12 post stem cell transplant

• In vitro immune tolerance

  Up to 2 years post stem cell transplant

Study Arms (1)

Lung and Bone Marrow Transplantation

EXPERIMENTAL

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; Drug: Rituximab; Drug: Alemtuzumab; Drug: Fludarabine; Drug: Thiotepa; Drug: G-CSF; Drug: Hydroxyurea

Interventions

CD3/CD19 negative hematopoietic stem cells BIOLOGICAL

Negative selection for CD3/CD19 will be performed on CliniMACS® depletion device and given at time no less than 8 weeks post lung transplantation

Lung and Bone Marrow Transplantation

Rituximab DRUG

Transplantation Conditioning

Also known as: Rituxan

Lung and Bone Marrow Transplantation

Alemtuzumab DRUG

Transplantation Conditioning

Also known as: Campath-1H

Lung and Bone Marrow Transplantation

Fludarabine DRUG

Transplantation Conditioning

Also known as: Fludara, Oforta

Lung and Bone Marrow Transplantation

Thiotepa DRUG

Transplantation Conditioning

Lung and Bone Marrow Transplantation

G-CSF DRUG

Transplantation conditioning

Also known as: Neupogen, Granix, Zarxio, Filgrastim

Lung and Bone Marrow Transplantation

Hydroxyurea DRUG

Transplantation Conditioning

Lung and Bone Marrow Transplantation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Patients must have evidence of end stage lung disease. Examples of such diseases include but are not limited to:
• Pulmonary Fibrosis
• COPD/Emphysema
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (2)

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15214, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Emphysema; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis

Interventions

Rituximab; Alemtuzumab; fludarabine; fludarabine phosphate; Thiotepa; Granulocyte Colony-Stimulating Factor; Filgrastim; Hydroxyurea

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Fibrosis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Urea; Amides

Central Study Contacts

Paul Szabolcs, M.D.

CONTACT

412-692-5427; Paul.Szabolcs@chp.edu

Shawna H McIntyre, RN

CONTACT

412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplantation and Cellular Therapy

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: April 18, 2018
• Study Start: April 19, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)