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

Phase 3RecruitingNCT04629833

medac GmbH210 enrolled

Overview

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) at Day 28 and/or overall survival (OS) until Visit Month 24 in adult and adolescent subjects with steroid-refractory acute graft-versus-host disease (SR-aGvHD).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

210

Conditions

Steroid-refractory Acute Graft-versus-host Disease

Interventions

MC0518BIOLOGICAL

MC0518 will be intravenously infused immediately after thawing.

BATBIOLOGICAL

BAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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, mammalian target of rapamycin (mTOR) 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).

Locations (42)

Outcomes

Primary Outcomes

Overall Response (OR)

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.

Time frame: Day 28

Overall Survival

Overall survival is defined as the time from randomization to the date of death due to any cause.

Time frame: Up to Month 24

Secondary Outcomes

Freedom from Treatment Failure (FFTF)

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.

Time frame: Up to 6 months

Acute Graft-versus-host Disease (aGvHD) Response

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.

Time frame: Days 28, 60, 100 and 180

Change from Baseline in aGvHD Grades

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.

Time frame: Baseline and Days 8, 15, 22, 28, 60, 100 and 180

Time to Response

Time to response is defined as the time from the date of the first treatment administration to the date of response.

Central Contacts

Clinical Trial Information

CONTACT

+49 40103 8006-0 ClinicalTrialInformation@medac.de

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud

Amiens, France

RECRUITING

CHU Jean Minjoz

Besançon, France

RECRUITING

Hopital Michallon

Grenoble, France

RECRUITING

CHRU Lille- Hopital Claude Huriez

Lille, France

RECRUITING

CHU de Nantes - Hotel Dieu

Nantes, France

RECRUITING

CHU de Nice Hopital Archet 1

Nice, France

RECRUITING

Centre Hospitalier Lyon Sud Pavillon Marcel Berard 1G

Pierre-Bénite, France

RECRUITING

Centre Hospitalier Universitaire CHU de Toulouse

Toulouse, France

RECRUITING

Hopitaux De Brabois

Vandœuvre-lès-Nancy, France

RECRUITING

Klinikum rechts der Isar

Munich, Bavaria, Germany

RECRUITING

...and 32 more locations

Time frame: Up to Month 24

Duration of Response

Duration is calculated from time from the first OR (CR or PR) until the time point of no aGvHD response in comparison to baseline.

Time frame: Up to Month 24

Best Overall Response (OR)

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.

Time frame: Up to Day 28

Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight

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.

Time frame: Up to Day 60 and Month 24

Number of Participants with Chronic Graft-versus-host Disease (cGvHD)

Number of participants with cGvHD will be reported.

Time frame: Day 60 to Month 24

Time to Chronic Graft-versus-host Disease (cGvHD)

Time to cGvHD is defined as the time between the last day of haematopoietic stem cell transplantation (HSCT) to the first episode of cGvHD.

Time frame: Day 60 to Month 24

Number of Participants with Graft Failure (GF)

Number of participants with GF will be reported.

Time frame: Up to Month 24

Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease

Number of participants with relapse or progression in participants with underlying malignant disease will be reported.

Time frame: Up to Month 24

Time to Relapse or Progression in Participants with Underlying Malignant Disease

Time to relapse or progression in participants with underlying malignant disease will be reported.

Time frame: Up to Month 24

Event-free survival (EFS)

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.

Time frame: Up to Month 24

Non-relapse Mortality (NRM)

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.

Time frame: Up to Month 24

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)

Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) by Severity

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.

Time frame: Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24)

Change from Baseline in Performance score based on Karnofsky scale (recipient age >= 16 years)

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.

Time frame: Baseline, Days 8, 15, 22, 28, 60 and 100

Change from Baseline in Performance score based on Lansky Scale

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.

Time frame: Baseline, Days 8, 15, 22, 28, 60 and 100

Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Health Status Index (HSI)

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).

Time frame: Baseline, Days 28, 60, 100 and 180

Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Visual Analogue Scale (VAS)

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).

Time frame: Baseline, Days 28, 60, 100 and 180

Change from Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Score

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.

Time frame: Baseline, Days 28, 60, 100 and 180