Last reviewed · How we verify

NCT02336230

A Prospective Study of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Participants Who Have Failed to Respond to Steroid Treatment for Acute Graft-Versus-Host Disease (aGVHD)

Completed Phase 3 Results posted Last updated 17 March 2022
What this trial tests

Phase 3 trial testing remestemcel-L in Grade B aGVHD in 55 participants. Completed in 9 April 2018.

Timeline
4 June 2015
Primary endpoint
9 April 2018
9 April 2018

Quick facts

Lead sponsorMesoblast, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment55
Start date4 June 2015
Primary completion9 April 2018
Estimated completion9 April 2018
Sites20 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Mesoblast, Inc. — full company profile →

Who can join

Adults 2 Months to 17, any sex, with Grade B aGVHD or Grade C aGVHD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy Primary · Day 28

ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.

GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg69.1
Overall Survival (OS) Rate at Day 100 Post Initiation of Therapy Secondary · Day 100

Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.

GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg74.5
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Responder Status at Day 28 Secondary · Day 100

Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.

Responders
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg86.8
Non- Responders
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg47.1
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Baseline aGVHD Grade Secondary · Day 100

OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. Maximum severity of acute GVHD was assessed by using International Bone Marrow Transplant Registry (IBMTR) index. The severity index was defined as: Grade A (skin Stage 1: extent of rash \<25%); Grade B (skin Stage 2: extent of rash 25 to 50% or liver Stage 1 to 2: total bilirubin 34 to 102 micromoles per liter \[mcmol/L\] or intestinal tract Stage 1 to 2: volume of diarrhea 550 to 1500 milliliters per day \[mL/day\]); Grade C (skin Stage 3: extent of rash \> 50%

Grade B
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg50.011.81 – 88.19
Grade C
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg82.661.22 – 95.05
Grade D
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg73.152.21 – 88.43
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Organ Involvement Secondary · Day 100

OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. The data was summarized for organ involvement: skin only, lower GI only, and multi-organ.

Skin Only
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg78.6
Lower GI Only
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg76.2
Multi-organ (Any Combination)
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg70.0
OR Rate at Day 56 and 100 Post Initiation of Therapy Secondary · Day 56 and Day 100

OR rate was defined as the percentage of participants who had achieved overall response. Overall response was defined as CR plus PR as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.

Day 56
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg58.2
Day 100
GroupValue95% CI
Remestemcel-L 2×10^6 MSCs/kg69.1

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline through 100 days of follow up. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Remestemcel-L 2×10^6 MSCs/kg
Serious: 35/54 (65%)
Deaths: 13/55

Serious adverse events (64 terms)

ReactionSystemRemestemcel-L 2×10^6 MSCs/kg
PyrexiaGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Pneumatosis intestinalisGastrointestinal disorders
Acute graft versus host diseaseImmune system disorders
Staphylococcal infectionInfections and infestations
Haemolytic uraemic syndromeBlood and lymphatic system disorders
Graft versus host disease in skinImmune system disorders
BK virus infectionInfections and infestations
Escherichia urinary tract infectionInfections and infestations
Human herpesvirus 6 infectionInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
DehydrationMetabolism and nutrition disorders
Acute myeloid leukaemia recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Posterior reversible encephalopathy syndromeNervous system disorders
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
HaemolysisBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Thrombotic microangiopathyBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Other adverse events (66 terms — click to expand)

ReactionSystemRemestemcel-L 2×10^6 MSCs/kg
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
Adenovirus infectionInfections and infestations
HypertensionVascular disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypotensionVascular disorders
Oedema peripheralGeneral disorders
Epstein-Barr viraemiaInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
Chronic graft versus host diseaseImmune system disorders
HypogammaglobulinaemiaImmune system disorders
HypomagnesaemiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
Adrenal insufficiencyEndocrine disorders
CushingoidEndocrine disorders
BK virus infectionInfections and infestations
Transaminases increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Cystitis haemorrhagicRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
HaematocheziaGastrointestinal disorders
Epstein-Barr virus infectionInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
AgitationPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
DysuriaRenal and urinary disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
TachycardiaCardiac disorders

Most-reported serious reactions: Pyrexia, Multiple organ dysfunction syndrome, Respiratory failure, Pneumatosis intestinalis, Acute graft versus host disease, Staphylococcal infection, Haemolytic uraemic syndrome, Graft versus host disease in skin.

Data from ClinicalTrials.gov NCT02336230 adverse events section.

Sponsor's own description

The study plans to treat at least 60 pediatric participants, male and female, between the ages of 2 months and 17 years inclusive with aGVHD following allogeneic hematopoietic stem cell transplant (HSCT) that has failed to respond to treatment with systemic corticosteroid therapy. Participants may have Grades C and D aGVHD involving the skin, liver and/or gastrointestinal (GI) tract or Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities.
    Galipeau J, Sensébé L. · · 2018 · cited 1288× · PMID 29859173 · DOI 10.1016/j.stem.2018.05.004
  2. Shattering barriers toward clinically meaningful MSC therapies.
    Levy O, Kuai R, Siren EMJ, Bhere D, et al · · 2020 · cited 501× · PMID 32832666 · DOI 10.1126/sciadv.aba6884
  3. Biological functions of mesenchymal stem cells and clinical implications.
    Naji A, Eitoku M, Favier B, Deschaseaux F, et al · · 2019 · cited 424× · PMID 31055643 · DOI 10.1007/s00018-019-03125-1
  4. Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range?
    Kabat M, Bobkov I, Kumar S, Grumet M. · · 2020 · cited 337× · PMID 31804767 · DOI 10.1002/sctm.19-0202
  5. Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress.
    Wu X, Jiang J, Gu Z, Zhang J, et al · · 2020 · cited 232× · PMID 32771052 · DOI 10.1186/s13287-020-01855-9
  6. Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses.
    Costa LA, Eiro N, Fraile M, Gonzalez LO, et al · · 2021 · cited 229× · PMID 32699947 · DOI 10.1007/s00018-020-03600-0
  7. Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?
    Galderisi U, Peluso G, Di Bernardo G. · · 2022 · cited 175× · PMID 34398443 · DOI 10.1007/s12015-021-10231-w
  8. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells.
    Elahi FM, Farwell DG, Nolta JA, Anderson JD. · · 2020 · cited 163× · PMID 31381842 · DOI 10.1002/stem.3061

Verify or expand the search:

Other trials of remestemcel-L

Trials testing the same drug.

Other Mesoblast, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02336230.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing