Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure

• Register: ClinicalTrials.gov
• Last refreshed on: 15 January 2024
• Main ID: NCT03500731
• Date of registration: 30/03/2018
• Prospective Registration: Yes
• Primary sponsor: Paul Szabolcs
• Public title: Lung and Bone Marrow Transplantation for Lung and Bone Marrow Failure
• Scientific title: Lung Transplant in Tandem With Bone Marrow Transplant for Combined Lung and Bone Marrow Failure
• Date of first enrolment: April 19, 2018
• Target sample size: 8
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03500731
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Paul Szabolcs, M.D.

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Emphysema or COPD

Intervention(s)

Drug: Rituximab

Drug: Thiotepa

Drug: Alemtuzumab

Drug: Fludarabine

Biological: CD3/CD19 negative hematopoietic stem cells

Drug: G-CSF

Drug: Hydroxyurea

Primary Outcome(s)

Restoration of blood cell count (in absence of growth factors) [Time Frame: at 12 months post stem cell transplant]

Myeloid chimerism [Time Frame: at 12 months post stem cell transplant]

BOS Score [Time Frame: at 1 year post lung transplant]

Engraftment failure [Time Frame: Up to 2 years post stem cell transplant]

Non-hematologic events [Time Frame: Up to 2 years post stem cell transplant]

Hematological events [Time Frame: after 30 days post stem cell transplant]

T-cell Chimerism [Time Frame: at 12 months post stem cell transplant]

Death [Time Frame: Up to 2 years post stem cell transplant]

Secondary Outcome(s)

Ability to withdrawal immunosuppression [Time Frame: By 1 year post stem cell transplant]

Long-term complications [Time Frame: Up to 2 years post stem cell transplant]

Prophylactic antimicrobial drugs [Time Frame: Up to 2 years post stem cell transplant]

Independence [Time Frame: up to 2 years post stem cell transplant]

Acute graft-versus-host-disease (GVHD) [Time Frame: Up to 2 years post stem cell transplant]

Feasibility of patients able to proceed to BMT within 6 months following lung transplantation [Time Frame: Up to 2 years post stem cell transplant]

Tolerance development to both host and pulmonary grafting [Time Frame: Up to 2 years post stem cell transplant]

Treatment antimicrobial drugs [Time Frame: up to 2 years post stem cell transplant]

Chronic lung allograft dysfunction [Time Frame: 1 year post lung transplant]

Time to withdraw immunosuppression [Time Frame: Up to 2 years post stem cell transplant]

Chronic graft-versus-host-disease (GVHD) [Time Frame: Up to 2 years post stem cell transplant]

Acute cellular rejection [Time Frame: Up to 2 years post stem cell transplant]

Secondary ID(s)

PRO17110400

Source(s) of Monetary Support

Please refer to primary and secondary sponsors