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Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (IDUNN)

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ClinicalTrials.gov Identifier: NCT04629833
Recruitment Status : Recruiting
First Posted : November 16, 2020
Last Update Posted : June 8, 2022
Sponsor:
Information provided by (Responsible Party):
medac GmbH

Brief Summary:
The primary purpose of this trial is to demonstrate the superiority of MC0518 compared to the first used best available therapy (BAT) with respect to overall response rate (ORR) in adult and adolescent participants with steroid-refractory acute graft-versus-host disease (SR-aGvHD) at Day 28.

Condition or disease Intervention/treatment Phase
Steroid-refractory Acute Graft-versus-host Disease Biological: MC0518 Biological: BAT Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised, Open-label, Multicentre, Phase 3 Trial of First-line Treatment With Mesenchymal Stromal Cells MC0518 Versus Best Available Therapy in Adult and Adolescent Subjects With Steroid-refractory Acute Graft-versus-host Disease After Allogeneic Haematopoietic Stem Cell Transplantation (IDUNN Trial)
Actual Study Start Date : August 16, 2021
Estimated Primary Completion Date : January 28, 2024
Estimated Study Completion Date : December 31, 2025


Arm Intervention/treatment
Experimental: MC0518
Participants will receive MC0518 1-2 million cells/ kilogram infusions (based on body weight at the Screening Visit) once a week for 4 weeks (Visit Day 1, 8, 15, and 22). Participants with partial response (PR) on Day 28 will have 2 additional MC0518 infusions administered on Day 29 and 36.
Biological: MC0518
MC0518 will be intravenously infused immediately after thawing.

Active Comparator: Best Available Therapy (BAT)
Participants will receive any one of the following systemic BATs based on the Investigator's decision: mycophenolate mofetil (MMF), extracorporeal photopheresis (ECP), anti-thymocyte globulin (ATG), everolimus, and ruxolitinib (RUX).
Biological: BAT
BAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision.




Primary Outcome Measures :
  1. Overall Response (OR) [ Time Frame: Day 28 ]
    OR is defined as complete response (CR) or partial response (PR) at Day 28 relative to aGvHD status at baseline. CR is defined as resolution of aGvHD in all involved organs. PR is defined as improvement in 1 stage in 1 or more organs involved with aGvHD symptoms without progression in others. Number of participants with OR will be reported.


Secondary Outcome Measures :
  1. Freedom from Treatment Failure (FFTF) [ Time Frame: Up to 6 months ]
    FFTF is defined as death, relapse or progression of the underlying disease, or addition or change to any further systemic immunosuppressive aGvHD therapy. Number of participants with FFTF will be reported.

  2. Overall Survival [ Time Frame: Up to Month 24 ]
    Overall survival is defined as the time from randomization to the date of death due to any cause.

  3. Acute Graft-versus-host Disease (aGvHD) Response [ Time Frame: Days 28, 60, 100 and 180 ]
    Number of participants with aGvHD response will be reported. aGvHD response will be categorized as OR (CR + PR), CR, PR, and NR. NR is defined as the absence of CR or PR.

  4. Change from Baseline in aGvHD Grades [ Time Frame: Baseline and Days 8, 15, 22, 28, 60, 100 and 180 ]
    aGvHD grades: Grade 0- no organ involvement (ie, Stage 0 skin, Stage 0 liver, and Stage 0 GI); Grade I-Stage 1 - 2 skin without liver/GI involvement; Grade II- Stage 3 skin and / or Stage 1 liver and / or Stage 1 GI; Grade III- Stage 2 - 3 liver and / or Stage 2 - 3 GI; Grade IV- Stage 4 skin and / or Stage 4 liver and/or Stage 4 GI.

  5. Time to Response [ Time Frame: Up to Month 24 ]
    Time to response is defined as the time from the date of the first treatment administration to the date of response.

  6. Duration of Response [ Time Frame: Up to Month 24 ]
    Duration is calculated from time from the first OR (CR or PR) until the time point of no aGvHD response in comparison to baseline.

  7. Best Overall Response (OR) [ Time Frame: Up to Day 28 ]
    Best OR is defined as the achievement of an OR at any time point up to and including Day 28. Number of participants with best OR will be reported.

  8. Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight [ Time Frame: Up to Day 60 and Month 24 ]
    The cumulative dose of steroids given for SR-aGvHD per kg of body weight from baseline until Day 60 and until Visit Month 24 will be analyzed.

  9. Number of Participants with Chronic Graft-versus-host Disease (cGvHD) [ Time Frame: Day 60 to Month 24 ]
    Number of participants with cGvHD will be reported.

  10. Time to Chronic Graft-versus-host Disease (cGvHD) [ Time Frame: Day 60 to Month 24 ]
    Time to cGvHD is defined as the time between the last day of haematopoietic stem cell transplantation (HSCT) to the first episode of cGvHD.

  11. Number of Participants with Graft Failure (GF) [ Time Frame: Up to Month 24 ]
    Number of participants with GF will be reported.

  12. Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease [ Time Frame: Up to Month 24 ]
    Number of participants with relapse or progression in participants with underlying malignant disease will be reported.

  13. Time to Relapse or Progression in Participants with Underlying Malignant Disease [ Time Frame: Up to Month 24 ]
    Time to relapse or progression in participants with underlying malignant disease will be reported.

  14. Event-free survival (EFS) [ Time Frame: Up to Month 24 ]
    EFS is defined as the time from the date of randomization to the date of the event. An event is defined as GF, relapse or progression of the underlying disease, or death due to any cause.

  15. Non-relapse Mortality (NRM) [ Time Frame: Up to Month 24 ]
    NRM is defined as the time from the date of randomisation to the date of the event. An event is defined as death without previous relapse or progression of the underlying disease.

  16. Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) [ Time Frame: Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24) ]
  17. Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) by Severity [ Time Frame: Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24) ]
    Severity will be graded based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening consequences; urgent intervention indicated; Grade 4- Death related to the AE.

  18. Change from Baseline in Performance score based on Karnofsky scale (recipient age >= 16 years) [ Time Frame: Baseline, Days 8, 15, 22, 28, 60 and 100 ]
    The Karnofsky performance score (KPS), which is reported on an ordinal scale from 0 to 100, provides a rough measure of the participant's well-being, including their ability to conduct activities of daily living and functional capacity. Higher score indicates normal, no complaints and no evidence of disease.

  19. Change from Baseline in Performance score based on Lansky Scale [ Time Frame: Baseline, Days 8, 15, 22, 28, 60 and 100 ]
    A Lansky score (recipient age greater than or equal to [>=] 1 years and less than [<] 16 years) will be recorded pre-treatment and measured serially at regular intervals after treatment. The score is a standard performance score that measures overall function of the child with a scale range from 0 to 100. Higher score indicates full activeness.

  20. Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Health Status Index (HSI) [ Time Frame: Baseline, Days 28, 60, 100 and 180 ]
    EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "TODAY". Responses were used to generate a HSI. HSI ranges from 0 (dead) to 1.00 (full health).

  21. Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Visual Analogue Scale (VAS) [ Time Frame: Baseline, Days 28, 60, 100 and 180 ]
    EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).

  22. Change from Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Score [ Time Frame: Baseline, Days 28, 60, 100 and 180 ]
    The FACT-BMT questionnaire was designed to measure the quality of life in subjects undergoing bone marrow (BM) transplantation. It consists of the following categories of assessment: physical well-being, social / family well-being, emotional well-being, functional well-being, and additional miscellaneous concerns that the subject may have concerning their healthcare, persons involved in their life, and other emotions and incapabilities. Score ranges from 0-164, with higher score indicating better quality of life.



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant had a previous allogeneic HSCT as indicated for non-malignant (including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies, and bone marrow failure syndromes) or haematological malignant disease, irrespective of human leukocyte antigen match
  • Participant has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit
  • Participant has experienced failure of previous first-line aGvHD treatment (ie, SR-aGvHD), defined as: a) aGvHD progression within 3 to 5 days of therapy onset with >= 2 mg/kg/day of prednisone equivalent or b) failure to improve within 5 to 7 days of treatment initiation with >= 2 mg/kg/day of prednisone equivalent or c) incomplete response after > 28 days of immunosuppressive treatment including at least 5 days with >= 2 mg/kg/day of prednisone equivalent
  • Participant has an estimated life expectancy > 28 days at the Screening Visit
  • Male or female participant who is >= 12 years of age at the Screening Visit

Exclusion Criteria:

  • Participant has overt relapse or progression or persistence of the underlying disease at the Screening Visit
  • Participant has received the last HSCT for a solid tumour disease
  • Participant has GvHD overlap syndrome at the Screening Visit
  • Participant has received systemic first-line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), methotrexate (MTX), and or cyclophosphamide before the Screening Visit
  • Participant has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit
  • Participant has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit (compliance to be confirmed for the period between the Screening Visit and the Baseline Visit at the Baseline Visit).

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): NCT04629833


Locations
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Sponsors and Collaborators
medac GmbH
Investigators
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Study Director: Jolanda Neele Syneos Health
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Responsible Party: medac GmbH
ClinicalTrials.gov Identifier: NCT04629833    
Other Study ID Numbers: MC-MSC.1/aGvHD
First Posted: November 16, 2020    Key Record Dates
Last Update Posted: June 8, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases