Cystic FibrosisPhase 1CEASE-CFNCT02866721
Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis
A Phase 1 study testing Mesenchymal Stem Cells in people with Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
This study is being done to test if it is safe to give stem cells to adult patients with Cystic Fibrosis (CF). The kind of stem cells we are studying are called allogeneic human mesenchymal stem cells or MSCs. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Aug 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1. CF subject enrolled in the main study and consented to this optional procedure
- Exclusion Criteria for both Healthy Volunteer (HV) Donors and CF Donors:
- Fever or current illness on the day of the cell collection
- Evidence of communicable disease
- Any significant change in health status within 2 weeks prior to cell collection that the Principal Investigator/Sub-Investigator deems relevant to exclude participation
- Subject reported history of organ transplantation
Show all 11Show fewer
- Subject reported history of human immunodeficiency virus, hepatitis B or C, or syphilis
- For HV donors only, subject-reported known history of being diagnosed with cystic fibrosis (CF) or being a CF carrier (one copy of CF gene mutation)
- Positive screening blood test result for any infectious disease.
- For HV donors only, positive test result for CMV or a CF gene mutation.
- Pregnant, planning a pregnancy, or breast-feeding at screening
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
Official title: A Phase I, Single Center, Open Label, Single Dose, Dose Escalation Study Assessing the Safety and Tolerability of AllogeneiC MEsenchymAl Stem CEll Infusion in Adults With Cystic Fibrosis-CEASE CF
This study is being done to test if it is safe to give stem cells to adult patients with Cystic Fibrosis (CF). The kind of stem cells we are studying are called allogeneic human mesenchymal stem cells or MSCs. MSCs are cells in the body that can grow into different types of cells and respond to various environmental situations. Allogeneic means the cells come from another person (a donor).
This study is only looking at whether or not it is safe to give the stem cells to adults with CF and how the infusion is tolerated. In the future, other studies may be done to see if stem cells can be a new therapeutic treatment for CF.
Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require approval from the U.S. Food and Drug Administration (FDA) before they can be marketed. The FDA has not approved any stem cell-based products for usual medical care, other than some specific blood forming stem cells for certain indications.
Read the detailed description
This will be a prospective, single-center, dose-escalation, open-label interventional study to evaluate the safety and tolerability of allogeneic human mesenchymal stem cells (hMSCs) in 15 clinically stable subjects with cystic fibrosis (CF) age ≥ 18 years. After a two to six week screening period, subjects will have a Baseline visit (Days 1-2) where they will undergo a single intravenous infusion of up to 5 x 10E6 allogeneic hMSCs/kilogram (hMSCs/kg) of body weight. Infusions will be performed in the Dahms Clinical Research Unit (DCRU) of University Hospitals Cleveland Medical Center. Subjects will be monitored for any infusion related toxicities for 24 hours after the infusion. Subsequent study visits will occur on Days 7, 14, 28, Months 3 and 6 and telephone calls will occur on Days 4 (or 5), 21, 56 and Month 12. Subject safety and tolerability of a single dose of hMSCs will be evaluated at study visits by review of subject diaries, interval history, pulmonary exacerbations, physical examination, spirometry, and analysis of safety laboratories. Special attention will be placed upon detecting pulmonary exacerbations because anti-inflammatory therapies theoretically could suppress the immune system to the point where it leads to increased infectious complications, although MSC therapeutics are proposed to be antimicrobial. In addition to evaluating safety, this study will also explore efficacy end-points for future clinical trials of MSCs in CF including inflammatory biomarkers from blood and sputum. Serum markers (calprotectin, myeloperoxidase (MPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1β (IL-1β), IL-6, IL8, IL-17, and tumor necrosis factor-a (TNF-a) and sputum markers (white cell counts and differentials, IL-1β, IL-6, IL-8, IL-10, IL-17, GM-CSF, macrophage inflammatory protein-3a (MIP- 3a), TNF-a, and active proteases including neutrophil elastase, alpha-1-antitrypsin, and matrix metallopeptidase 9 (MMP-9) will be determined at Baseline and on Days 7 and 28 for with-in subject comparison. All subject samples will be archived for future projects. Finally, a diagnostic bone marrow exam will be performed on subjects with CF who consent to undergo this optional procedure. Bone marrow samples will be banked and used for future translational studies.
- Conditions
- Cystic Fibrosis
- Being tested
- Mesenchymal Stem Cells
- Keywords
- Human Mesenchymal Stem Cells
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem CellsBiological
Also called MSCs
A single dose, one time infusion (in the vein) of one of the following doses of human mesenchymal stem cells (hMSCs): 1 x 10^6, 3 x 10^6 or 5 x 10^6 human mesenchymal stem cells per kilogram body weight (hMSCs/kg) during Visit 2. A traditional 3+3 design will be utilized.
Allogeneic mesenchymal stem cells (MSCs) will be derived from bone marrow aspirates from a healthy donor whose serum tests negative for cytomegalovirus (CMV) antibodies. Healthy donors will undergo tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs will be validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis lung infection and inflammation.
| Study group | Role | What they receive |
|---|---|---|
| Human Allogeneic Mesenchymal Stem Cells | Experimental | One time intravenous (IV) Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram of body weight (hMSCs/kg). A dose escalation using the "3+3" design will be employed. The three doses are 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There is no placebo group. All study participants will receive stem cells. Receives: Biological: Mesenchymal Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade ≥3 Infusion-related Allergic Toxicities
For this study, dose limiting toxicities included the emergence of infusion-related allergic adverse events as well as regimen related toxicities in the first 24 hours after hMSC infusion of a grade ≥ 3 as scored according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This is the number of participants who experienced a dose limiting toxicity during the study.
Measured: 24 hours post infusion
Number of Serious Adverse Events and Number of Non-Serious Adverse Events
Participants were followed for 12 months after human mesenchymal stem cell infusion. All events from the infusion date through the end of follow-up were included. This shows the total number of adverse events or serious adverse events occurring in each dosing cohort.
Measured: 1 year
Number of Pulmonary Exacerbations Requiring Intravenous Antibiotics
Participants were followed for 12 months after human mesenchymal stem cell infusion. All events occurring from the infusion date through the end of follow-up were included. This shows the number of pulmonary exacerbations requiring intravenous antibiotics in each dosing cohort.
Measured: 1 year
Forced Expiratory Volume in the First Second (FEV1) % Predicted at Baseline and 30 Minutes, 4 Hours, 24 Hours, 7 Days, 14 Days, 28 Days, 3 Months, 6 Months Post Human Mesenchymal Stem Cell Infusion.
Lung function was followed for 6 months post human mesenchymal stem cell infusion. This shows the mean forced expiratory volume in the first second (FEV1) percent predicted for each cohort throughout the study.
Measured: Baseline and 30 minutes, 4 hours, 24 hours, 7 days, 14 days, 28 days, 3 months, 6 months Post Human Mesenchymal Stem Cell Infusion
Secondary outcomes (16)
Serum Inflammatory Markers - Calportectin Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including Calprotectin were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for calportectin was 88.3 picogram per millilitre.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for GM-CSF was 2.6 picograms per milliliter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including interleukin -1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-1 was 13.1 picograms per milliliter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including interleukin -17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-17 was 13.5 picograms per milliliter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including interleukin -6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-6 was 13.5 picograms per milliliter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including interleukin -8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-8 was 13.9 picograms per milliliter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Myeloperoxidase (MPO) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including myeloperoxidase (MPO) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28
Serum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit of detection for TNF-a was 12.9 picograms per millilter.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including granulocyte-macrophage colony-stimulating factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including interleukin-1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-10 (IL-10) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including interleukin-10 (IL-10) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including interleukin-17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including interleukin-6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including interleukin-8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Macrophage Inflammatory Protein-3 Alpha (MIP-3a) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including macrophage inflammatory protein-3 alpha (MIP-3a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28
Sputum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown.
Measured: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2020
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Case Western Reserve University, Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Erica A. Roesch, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02866721
- Sponsor's protocol ID
- Protocol CF-MSC-01
- Other IDs
- DASENB15A0
- Acronym
- CEASE-CF
- Status last verified
- Jan 2023
- First submitted
- 7 Aug 2016
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9.
PubMed 20215542Inamdar AC, Inamdar AA. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell. Exp Lung Res. 2013 Oct;39(8):315-27. doi: 10.3109/01902148.2013.816803. Epub 2013 Aug 30.
PubMed 23992090Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012 Feb;18(2):128-34. doi: 10.1016/j.molmed.2011.10.004. Epub 2011 Nov 25.
PubMed 22118960Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559. Epub 2012 Oct 25.
PubMed 23133515Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009 Jan;217(2):318-24. doi: 10.1002/path.2469.
PubMed 19023885Bonfield TL, Caplan AI. Adult mesenchymal stem cells: an innovative therapeutic for lung diseases. Discov Med. 2010 Apr;9(47):337-45.
PubMed 20423678Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013 Sep 4;4:201. doi: 10.3389/fimmu.2013.00201.
PubMed 24027567Antunes MA, Laffey JG, Pelosi P, Rocco PR. Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem. 2014 Jun;115(6):1023-32. doi: 10.1002/jcb.24783.
PubMed 24515922Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. doi: 10.4049/jimmunol.179.3.1855.
PubMed 17641052Sutton MT, Fletcher D, Ghosh SK, Weinberg A, van Heeckeren R, Kaur S, Sadeghi Z, Hijaz A, Reese J, Lazarus HM, Lennon DP, Caplan AI, Bonfield TL. Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment. Stem Cells Int. 2016;2016:5303048. doi: 10.1155/2016/5303048. Epub 2016 Jan 26.
PubMed 26925108
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single Center, Open Label, Single Dose, Dose Escalation Study Assessing the Safety and Tolerability of AllogeneiC MEsenchymAl Stem CEll Infusion in Adults With Cystic Fibrosis-CEASE CF
- ClinicalTrials.gov ID
- NCT02866721
- Acronym / sponsor ID
- CEASE-CF / Protocol CF-MSC-01
- Conditions
- Cystic Fibrosis
- Keywords
- Human Mesenchymal Stem Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Collaborators
- Case Western Reserve University, Cystic Fibrosis Foundation
- Study start
- Aug 2016 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 15 Aug 2016 (estimated)
- Results
- Posted 30 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to test if it is safe to give stem cells to adult patients with Cystic Fibrosis (CF). The kind of stem cells we are studying are called allogeneic human mesenchymal stem cells or MSCs. MSCs are cells in the body that can grow into different types of cells and respond to various environmental situations. Allogeneic means the cells come from another person (a donor).
This study is only looking at whether or not it is safe to give the stem cells to adults with CF and how the infusion is tolerated. In the future, other studies may be done to see if stem cells can be a new therapeutic treatment for CF.
Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require approval from the U.S. Food and Drug Administration (FDA) before they can be marketed. The FDA has not approved any stem cell-based products for usual medical care, other than some specific blood forming stem cells for certain indications.
Detailed description
This will be a prospective, single-center, dose-escalation, open-label interventional study to evaluate the safety and tolerability of allogeneic human mesenchymal stem cells (hMSCs) in 15 clinically stable subjects with cystic fibrosis (CF) age ≥ 18 years. After a two to six week screening period, subjects will have a Baseline visit (Days 1-2) where they will undergo a single intravenous infusion of up to 5 x 10E6 allogeneic hMSCs/kilogram (hMSCs/kg) of body weight. Infusions will be performed in the Dahms Clinical Research Unit (DCRU) of University Hospitals Cleveland Medical Center. Subjects will be monitored for any infusion related toxicities for 24 hours after the infusion. Subsequent study visits will occur on Days 7, 14, 28, Months 3 and 6 and telephone calls will occur on Days 4 (or 5), 21, 56 and Month 12. Subject safety and tolerability of a single dose of hMSCs will be evaluated at study visits by review of subject diaries, interval history, pulmonary exacerbations, physical examination, spirometry, and analysis of safety laboratories. Special attention will be placed upon detecting pulmonary exacerbations because anti-inflammatory therapies theoretically could suppress the immune system to the point where it leads to increased infectious complications, although MSC therapeutics are proposed to be antimicrobial. In addition to evaluating safety, this study will also explore efficacy end-points for future clinical trials of MSCs in CF including inflammatory biomarkers from blood and sputum. Serum markers (calprotectin, myeloperoxidase (MPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1β (IL-1β), IL-6, IL8, IL-17, and tumor necrosis factor-a (TNF-a) and sputum markers (white cell counts and differentials, IL-1β, IL-6, IL-8, IL-10, IL-17, GM-CSF, macrophage inflammatory protein-3a (MIP- 3a), TNF-a, and active proteases including neutrophil elastase, alpha-1-antitrypsin, and matrix metallopeptidase 9 (MMP-9) will be determined at Baseline and on Days 7 and 28 for with-in subject comparison. All subject samples will be archived for future projects. Finally, a diagnostic bone marrow exam will be performed on subjects with CF who consent to undergo this optional procedure. Bone marrow samples will be banked and used for future translational studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Human Allogeneic Mesenchymal Stem Cells | Experimental | Biological: Mesenchymal Stem CellsOne time intravenous (IV) Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram of body weight (hMSCs/kg). A dose escalation using the "3+3" design will be employed. The three doses are 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There is no placebo group. All study participants will receive stem cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. CF subject enrolled in the main study and consented to this optional procedure
- Fever or current illness on the day of the cell collection
- Evidence of communicable disease
- Any significant change in health status within 2 weeks prior to cell collection that the Principal Investigator/Sub-Investigator deems relevant to exclude participation
- Subject reported history of organ transplantation
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal Stem CellsAlso: MSCsA single dose, one time infusion (in the vein) of one of the following doses of human mesenchymal stem cells (hMSCs): 1 x 10^6, 3 x 10^6 or 5 x 10^6 human mesenchymal stem cells per kilogram body weight (hMSCs/kg) during Visit 2. A traditional 3+3 design will be utilized. Allogeneic mesenchymal stem cells (MSCs) will be derived from bone marrow aspirates from a healthy donor whose serum tests negative for cytomegalovirus (CMV) antibodies. Healthy donors will undergo tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs will be validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis lung infection and inflammation. | Biological | Human Allogeneic Mesenchymal Stem Cells |
Primary outcome
Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade ≥3 Infusion-related Allergic Toxicities
Time frame: 24 hours post infusion
For this study, dose limiting toxicities included the emergence of infusion-related allergic adverse events as well as regimen related toxicities in the first 24 hours after hMSC infusion of a grade ≥ 3 as scored according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This is the number of participants who experienced a dose limiting toxicity during the study.
Number of Serious Adverse Events and Number of Non-Serious Adverse Events
Time frame: 1 year
Participants were followed for 12 months after human mesenchymal stem cell infusion. All events from the infusion date through the end of follow-up were included. This shows the total number of adverse events or serious adverse events occurring in each dosing cohort.
Number of Pulmonary Exacerbations Requiring Intravenous Antibiotics
Time frame: 1 year
Participants were followed for 12 months after human mesenchymal stem cell infusion. All events occurring from the infusion date through the end of follow-up were included. This shows the number of pulmonary exacerbations requiring intravenous antibiotics in each dosing cohort.
Forced Expiratory Volume in the First Second (FEV1) % Predicted at Baseline and 30 Minutes, 4 Hours, 24 Hours, 7 Days, 14 Days, 28 Days, 3 Months, 6 Months Post Human Mesenchymal Stem Cell Infusion.
Time frame: Baseline and 30 minutes, 4 hours, 24 hours, 7 days, 14 days, 28 days, 3 months, 6 months Post Human Mesenchymal Stem Cell Infusion
Lung function was followed for 6 months post human mesenchymal stem cell infusion. This shows the mean forced expiratory volume in the first second (FEV1) percent predicted for each cohort throughout the study.
16 secondary outcomes
Serum Inflammatory Markers - Calportectin Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Myeloperoxidase (MPO) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Serum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-10 (IL-10) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Macrophage Inflammatory Protein-3 Alpha (MIP-3a) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Sputum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28
Time frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20215542Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9.
- Background: PubMed 23992090Inamdar AC, Inamdar AA. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell. Exp Lung Res. 2013 Oct;39(8):315-27. doi: 10.3109/01902148.2013.816803. Epub 2013 Aug 30.
- Background: PubMed 22118960Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012 Feb;18(2):128-34. doi: 10.1016/j.molmed.2011.10.004. Epub 2011 Nov 25.
- Background: PubMed 23133515Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559. Epub 2012 Oct 25.
- Background: PubMed 19023885Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009 Jan;217(2):318-24. doi: 10.1002/path.2469.
- Background: PubMed 20423678Bonfield TL, Caplan AI. Adult mesenchymal stem cells: an innovative therapeutic for lung diseases. Discov Med. 2010 Apr;9(47):337-45.
- Background: PubMed 24027567Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013 Sep 4;4:201. doi: 10.3389/fimmu.2013.00201.
- Background: PubMed 24515922Antunes MA, Laffey JG, Pelosi P, Rocco PR. Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem. 2014 Jun;115(6):1023-32. doi: 10.1002/jcb.24783.
- Results publication: PubMed 17641052Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. doi: 10.4049/jimmunol.179.3.1855.
- Results publication: PubMed 26925108Sutton MT, Fletcher D, Ghosh SK, Weinberg A, van Heeckeren R, Kaur S, Sadeghi Z, Hijaz A, Reese J, Lazarus HM, Lennon DP, Caplan AI, Bonfield TL. Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment. Stem Cells Int. 2016;2016:5303048. doi: 10.1155/2016/5303048. Epub 2016 Jan 26.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erica A. Roesch, MD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesenchymal Stem Cells in people with Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade ≥3 Infusion-related Allergic Toxicities (time frame: 24 hours post infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02866721, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.