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Trial record 3 of 86 for:    stop cystic fibrosis

Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis (CEASE-CF)

This study is currently recruiting participants.
Verified March 2017 by James F. Chmiel, University Hospitals Cleveland Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02866721
First Posted: August 15, 2016
Last Update Posted: March 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Case Western Reserve University
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
James F. Chmiel, University Hospitals Cleveland Medical Center
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis Biological: Mesenchymal Stem Cells Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by James F. Chmiel, University Hospitals Cleveland Medical Center:

Primary Outcome Measures:
  • Dose limiting toxicity (DLT), triggered by occurrence in the first 24 hours after hMSC infusion of grade ≥3 infusion-related allergic toxicities [ Time Frame: 24 hours ]
  • Incidence and severity of adverse events [ Time Frame: 1 year ]
  • Number of pulmonary exacerbations [ Time Frame: 1 year ]
  • Diary reports (Cystic Fibrosis Respiratory Symptom Diary (CFRSD)) [ Time Frame: 35 days ]
  • Changes in subject reported symptoms as captured by the Respiratory Signs and Symptoms Questionnaire (RSSQ) from Baseline (Visit 2) Day 1 to Baseline (Visit 2) Day 2, Visits 3, 4, 5, 6 and 7 and at times when a pulmonary exacerbation is being considered [ Time Frame: 1 year ]
  • Changes in physical examination [ Time Frame: 28 days ]
  • Changes in vital signs including oxygen saturation checked throughout infusion [ Time Frame: 24 hours ]
  • Changes in spirometry (FEV1 %, FEV1 (Liters), FEF25-75) determined 30 minutes, 4 hours, and 24 hours after completion of infusion and from Baseline (Visit 2) Day 1 to Visits 3, 4, 5, 6 and 7 [ Time Frame: 6 months ]
  • Change in sputum quantitative microbiology (bacterial colony forming units between Baseline to Day 7 and Day 28) [ Time Frame: 28 days ]
  • Changes in hematology, comprehensive chemistry, ESR, hs-CRP, and urinalysis results [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Change in blood inflammatory biomarkers from Baseline to Day 7 and Day 28 [ Time Frame: 28 days ]
  • Change in sputum inflammatory biomarkers from Baseline to Day 7 and Day 28 [ Time Frame: 28 days ]

Estimated Enrollment: 15
Study Start Date: August 2016
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Human Allogeneic Mesenchymal Stem Cells
One time IV Infusion of up to 5 x 10^6 allogeneic hMSCs/kg of body weight. 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.
Biological: Mesenchymal Stem Cells

A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design will be utilized.

Allogeneic 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 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 CF lung infection and inflammation.

Other Name: MSCs

Detailed Description:
This will be a prospective, single-center, dose-escalation, open-label interventional study to evaluate the safety and tolerability of allogeneic hMSCs in 15 clinically stable subjects with 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 10EE6 allogeneic 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, MPO, GM-CSF, IL-1β, IL-6, IL8, IL-17, and TNF-a) and sputum markers (white cell counts and differentials, IL-1β, IL-6, IL-8, IL-10, IL-17, GM-CSF, MIP- 3a, TNF-a, and active proteases including neutrophil elastase, a1-anti-trypsin, and 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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

CF Subject Inclusion Criteria:

  1. Male or female 18 to 40 years of age
  2. Confirmed diagnosis of CF as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following criteria:

    1. Sweat chloride equal to or greater than 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT)
    2. 2 well-characterized, disease causing mutations in the CFTR gene
  3. Clinically stable with no significant changes in health status within 2 weeks prior to screening.
  4. FEV1 ≥ 50% & ≤ 100% predicted for age based on the global lung function initiative equations at the screening visit
  5. Weight ≥ 40 kg at the screening visit
  6. Able to perform repeatable, consistent efforts in pulmonary function testing
  7. Written informed consent obtained from the subject.

CF Subject Exclusion Criteria:

  1. Use of an investigational agent within the 4-week period prior to Visit 1 (Day -42 to -10)
  2. Chronic daily (>10 mg) or alternate daily (>20 mg on alternate days) use of systemic corticosteroids within the 4 weeks prior to Visit 1 (Day -42 to -10) or initiation of any dosage of systemic corticosteroids within 72 hours prior to Visit 2 (Day 1).
  3. Use of hydroxychloroquine or immunosuppressants.
  4. Initiation of a new antibiotic (oral, IV, and/or inhaled) that is not part of the subject's maintenance regimen for treatment of acute respiratory symptoms within 2 weeks prior to screening through Visit 2 (Day 1)
  5. Initiation of any new chronic therapy (e.g., Pulmozyme®, hypertonic saline, Kalydeco®, Orkambi®, high-dose ibuprofen azithromycin, TOBI®, Cayston®, nebulized colistiin, bronchodilators, inhaled corticosteroids, etc.) within 4 weeks prior to screening
  6. Active treatment for non-tuberculous Mycobacteria
  7. History of a sputum culture positive for a Burkholderia cepacia complex organism in the previous 12 months.
  8. Current tobacco smoker
  9. Oxygen saturation < 92% on room air at Visit 1 (Day -42 to -10)
  10. History of pulmonary hypertension
  11. SGOT (ALT) or SGPT (AST) > 2.5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension
  12. Total bilirubin concentration > 1.2 mg/dL at screening
  13. Creatinine > 1.8 mg/dL at screening
  14. Pregnant, breastfeeding, or unwilling to practice birth control between Visit 2 (Day 1) and Telephone Call 3 (Day 56) (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal
  15. Screening hematology with white blood cell count < 4.5 x 109 cells/L, hematocrit < 30%, and platelets < 150 x 109 platelets/L
  16. History of invasive cancer requiring systemic therapy
  17. History of organ transplantation
  18. Currently listed for lung transplantation or having potential to be listed for lung transplantation in the succeeding 12 calendar months from screening
  19. Subject unlikely to complete the study as determined by the Investigator

Inclusion Criteria for Healthy Volunteer Donors:

  1. Male/female age ≥ 18 years to ≤ 40 years
  2. Able to understand and sign ICF (a legally authorized representative will not be permitted)

Inclusion Criteria for CF Donors:

1. CF subject enrolled in the main study and consented to this optional procedure

Exclusion Criteria for both Healthy Volunteer Donors and CF Donors:

  1. Fever or current illness on the day of the cell collection
  2. Evidence of communicable disease
  3. Any significant change in health status within 2 weeks prior to cell collection that the PI/Sub-Investigator deems relevant to exclude participation
  4. Subject reported history of organ transplantation
  5. Subject reported history of HIV, hepatitis B or C, or syphilis
  6. 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)
  7. Positive screening blood test result for any infectious disease.
  8. For HV donors only, positive test result for CMV or a CF gene mutation.
  9. Pregnant, planning a pregnancy, or breast-feeding at screening
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02866721


Contacts
Contact: Ellen Divoky, CCRP (216) 844-3248 Ellen.Divoky@UHhospitals.org
Contact: Kathleen A Hilliard, CCRC (216) 844-7489 Kathleen.Hilliard@UHhospitals.org

Locations
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Kathleen A Hilliard, CCRC    216-844-7489    Kathleen.Hilliard@UHhospitals.org   
Principal Investigator: James F. Chmiel, MD, MPH         
Sponsors and Collaborators
James F. Chmiel
Case Western Reserve University
Cystic Fibrosis Foundation Therapeutics
Investigators
Principal Investigator: James F Chmiel, MD, MPH University Hospitals Cleveland Medical Center
  More Information

Publications:

Responsible Party: James F. Chmiel, Professor of Pediatrics, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT02866721     History of Changes
Other Study ID Numbers: Protocol CF-MSC-01
DASENB15A0 ( Other Grant/Funding Number: Cystic Fibrosis Foundation Therapeutics )
First Submitted: August 7, 2016
First Posted: August 15, 2016
Last Update Posted: March 13, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by James F. Chmiel, University Hospitals Cleveland Medical Center:
Human Mesenchymal Stem Cells

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases