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Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (ASSIST-CLAD)

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ClinicalTrials.gov Identifier: NCT02709343
Recruitment Status : Recruiting
First Posted : March 16, 2016
Last Update Posted : October 4, 2018
Sponsor:
Collaborators:
Isopogen
Cell and Tissue Therapies
Information provided by (Responsible Party):
Daniel Chambers, The University of Queensland

Brief Summary:
This study is designed for lung transplant patients who have developed chronic lung allograft dysfunction (CLAD). Consented patients will receive 4 intravenous doses of allogeneic, bone-marrow-derived MSCs (2*10^6 cells/kg/dose) or matching placebo over a period of 2 weeks with a 12 month follow up.

Condition or disease Intervention/treatment Phase
Chronic Lung Allograft Dysfunction (CLAD) Drug: Bone-marrow derived MSCs Drug: Placebo Phase 2

Detailed Description:
This is a phase 2, multi-center, randomized study (n=82, 1:1 MSC:placebo) where consented patients will receive 4 intravenous doses of IMP over a period of 2 weeks. Patients must provide written informed consent and meet the all Inclusion Criteria and none of the Exclusion Criteria to be eligible. Screening procedures include obtaining medical history, current medications, questionnaires, vital signs, Chest Xray, 6 Minute walk test and blood tests. Historical chest CT and full lung function from 12 weeks prior to screening may be used. Bronchoscopy with biopsy must have been performed no more than 6 months prior to screening. A bronchoscopy with bronchoalveolar lavage (BAL) is required, however will not need to be repeated if performed within 14 days prior to the baseline visit. Patients will then receive 4 infusions of MSC/placebo over a period of 2 weeks, with follow up at Week 3,6,10,14,28,41 and week 54.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2 Randomised Controlled Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (CLAD)
Actual Study Start Date : April 21, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Arm Intervention/treatment
Experimental: Bone-marrow derived MSCs
4 doses of Allogeneic bone-marrow derived MSCs (2x106 cells/kg) given intravenously twice weekly for 2 weeks
Drug: Bone-marrow derived MSCs
Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells
Other Name: MSC

Placebo Comparator: Placebo
Placebo product manufactured to look like MSCs
Drug: Placebo
Placebo product visually very similar to mesenchymal stromal cells




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: From baseline to week 54 ]
    Progression-free survival is a composite end-point of freedom from CLAD progression or death from any-cause. CLAD progression is defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1 to the 12 month (week 54) visit.


Secondary Outcome Measures :
  1. Time to fall in FEV1 > 10% [ Time Frame: From the baseline (screening) visit ]
    Defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1

  2. Freedom from Bronchiolitis Obliterans Syndrome (BOS) grade 3 [ Time Frame: Week 54 ]
    BOS grade 3 is defined as FEV1 <50% of the best-post-transplant FEV1

  3. All cause mortality [ Time Frame: Week 54 ]
  4. CLAD-specific mortality [ Time Frame: Week 54 ]
    Defined as any death felt by the investigator to be at least partially related to CLAD.

  5. Freedom from acute rejection [ Time Frame: From baseline to week 54 ]
    Acute rejection defined as any biopsy proven episode of acute vascular (A1-A4) or airway (B1R or B2R) rejection.

  6. Freedom from the development of new donor specific anti-HLA antibodies [ Time Frame: From baseline to week 14 ]
    An anti-HLA antibody (any mean fluorescent intensity level) with specificity for a donor HLA type at 3 months which was not present prior to IMP treatment

  7. Freedom from CLAD progression [ Time Frame: From baseline to week 54 ]
    CLAD progression is defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1 at 12 months.

  8. Rate of FEV1 decline [ Time Frame: From baseline to week 54 ]
    Rate of FEV1 decline is defined as the slope of the regression line for FEV1 between the screening visit and week 54

  9. Rate of FVC decline [ Time Frame: From baseline to week 54 ]
    Rate of FVC decline is defined as the slope of the regression line for FVC between the screening visit and week 54

  10. Change in 6-minute walk distance (6MWD) [ Time Frame: From baseline to week 54 ]
    Change in 6MWD is defined as the difference between the 6MWD at screening and the week 54 visit. Patients who have died by week 54 will receive a 6MWD of 0.

  11. Change in St George's Respiratory Questionnaire (SGRQ) Score [ Time Frame: From baseline to week 54 ]
    Change in SGRQ is defined as the difference between the total SGRQ at screening and the week 54 visit. Patients who have died by week 54 will receive a SGRQ of 0.

  12. Inpatient bed-days [ Time Frame: From baseline to week 54 ]
    This is defined as the aggregate of inpatient bed-days between the screening visit and week 54.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Bilateral lung transplant recipients aged ≥ 18 years and at least 6 months post-transplant. Patients with other organs transplanted (eg heart, liver, kidney) or those who have undergone lobar transplantation, or re-transplantation, are potentially eligible.
  2. New-onset CLAD (defined as a persistent (3weeks apart) fall in FEV1 of at least 20% from the mean of the two best post-transplant values taken at least 3 weeks apart) in the 12 months prior to the screening visit. Other causes of a fall in FEV1 (acute cellular or humoral rejection, active infection, anastomotic stenosis etc.) must be excluded as per international guidelines.
  3. Stable immunosuppression regimen, as assessed by the investigator, in the 8 weeks prior to the screening visit.
  4. Available for all specified assessments at the study site through the completion of the study, including the protocol bronchoscopies.
  5. Provision of written informed consent.

Exclusion Criteria:

  1. Any condition that in the opinion of the Investigator may interfere with the safety of the patient, his / her completion of required follow-up visits or evaluation of the study objectives
  2. Untreated cellular or humoral rejection
  3. Clinically meaningful and untreated viral, bacterial or fungal infection
  4. Use of azithromycin or another macrolide antibiotic, if commenced within 8 weeks of the screening visit
  5. Intravenous pulsed methylprednisolone, within 4 weeks of the screening visit
  6. Use of extracorporeal photopheresis, within 4 weeks of the screening visit
  7. Use of total lymphoid irradiation, within 4 weeks of the screening visit
  8. Poor functional status not expected to survive 6 months
  9. Allergy to beef products
  10. Women who are pregnant, breast-feeding or unwilling to use adequate contraception
  11. Patients who are currently participating in another interventional clinical trial

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): NCT02709343


Contacts
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Contact: Daniel Chambers, MBBS MD +61 7 3139 4000 daniel.chambers@health.qdl.gov.au

Locations
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Australia, New South Wales
St Vincents Hospital Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Alan Glanville, MBBS MD    02 8382 3257    Allan.Glanville@svha.org.au   
Australia, Queensland
The Prince Charles Hospital Not yet recruiting
Brisbane, Queensland, Australia, 4032
Contact: Daniel Chambers, MBBS MD    +61 7 3139 4000    Daniel.Chambers@health.qld.gov.au   
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5000
Contact: Chien-Li Holmes-Liew, MBBS FRACP    +61 8 8222 4000    chien-li.holmes-liew@health.sa.gov.au   
Australia, Victoria
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Glen Westall, MBBS PhD    +61 3 9076 2000    g.westall@alfred.org.au   
Australia, Western Australia
Fiona Stanley Hospital Recruiting
Murdoch, Western Australia, Australia, 6150
Contact: Michael Musk, MBBS FRACP    08 6152 0860    mike.musk@health.wa.gov.au   
Sponsors and Collaborators
The University of Queensland
Isopogen
Cell and Tissue Therapies
Investigators
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Principal Investigator: Daniel Chambers, MBBS MD University of Queensland & The Prince Charles Hospital

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Responsible Party: Daniel Chambers, A/Prof Daniel Chambers, The University of Queensland
ClinicalTrials.gov Identifier: NCT02709343     History of Changes
Other Study ID Numbers: ASSIST-CLAD
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data will be analysed and shared with collaborators with the plan to publish the results.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No