- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02359929
BMT Autologous MSCs for GvHD
A Phase I Study of Mesenchymal Stromal Cells for the Treatment of Acute and Chronic Graft Versus Host Disease
Subjects in this study have had an allogeneic (blood or marrow cells from another person) blood or marrow transplant to treat leukemia, lymphoma or other cancer of the blood, and have now developed Graft Versus Host Disease (GVHD) that is not responding to standard treatment. GVHD is when the graft (transplanted bone marrow or blood) attacks the recipient's body. GVHD occurs early after transplant (acute) and/or sometimes months after transplant (chronic). Both forms can be life threatening; chronic GVHD can be a lifelong disabling condition.
Mesenchymal stromal cells (MSCs) exist in tissues throughout the body. One place they are found is in the bone marrow and from here they can be obtained by needle aspiration, the same way bone marrow samples are obtained to test for leukemia. This study uses autologous MSCs obtained from the recipient with acute and/or chronic GVHD, which have a lower chance of being rejected. These MSCs may promote tolerance, helping the donor immune cells accept the recipient's body.
This trial is being conducted as a step toward testing the long-term hypothesis that freshly cultured autologous MSC grown in platelet lysate-containing medium will modulate donor T-cell immune responses and reduce GVHD in allo-HSCT recipients. As a phase I dose escalation trial of autologous MSC in patients with acute and chronic GVHD, the main aim is to evaluate the safety of this therapy and its effects on GVHD biomarkers and T-cell phenotype
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
EPIC MSC2014-002 solution- Autologous Mesenchymal Stromal Cells expanded using pooled human platelet lysate,is made up of autologous marrow-derived mesenchymal stromal cells ex vivo expanded numerically for approximately 14 days using pooled human Platelet Lysate (phPL), harvested from culture on the day of infusion and suspended at a concentration of 4 million cells/ml in Plasmalyte A with 0.5% human serum albumin. This is a phase I dose-escalation, open label, non-randomized, non-placebo controlled, single group assignment study to evaluate the safety and tolerability of EPIC MSC2014-002. The product will be infused intravenously and will be administered at one of three dose levels: (Dose level 1): Single Cell infusion 2 x 10^6 cells/kg, (Dose Level 2): Two weekly Cell infusions 2 x 10^6 cells/kg , (Dose level 3): Four weekly Cell infusion 2 x 10^6 cells/kg. This Phase I clinical trial will enroll 12-24 subjects with acute or chronic GVHD. The duration of this study for each patient is 1 year. The investigators anticipate that this study will be completed within 3 years of commencement.
Objectives:
- To determine the safety and tolerability of infusing escalating doses of autologous MSCs for patients with acute or chronic GVHD.
- To assess the overall response rate of acute and chronic GVHD to autologous MSC infusion. These data will be used to plan future, larger clinical trials to evaluate the efficacy of autologous MSCs for the treatment of GVHD.
- To determine the effect of MSC infusion on lymphocyte phenotype, inflammatory biomarkers and GVHD specific biomarker levels
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta/Emory University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age: patients must be ≥12 years old and weigh > (25 kg) at the time of study entry.
- Patients must have received an allogeneic stem cell transplant for a hematologic malignancy.
- Must have one of the following diagnoses:
- Acute GVHD (grade II-IV) requiring systemic therapy and refractory/unresponsive to glucocorticoid (>1 mg prednisone-equivalent/kg x 1 week)
- Chronic GVHD that is extensive and not improved despite therapy with glucocorticoid (> 0.5 mg prednisone-equivalent/kg/day) and therapeutic doses of a calcineurin inhibitor for at least 4 weeks, or worsened within 2 weeks, or overlap syndrome not responding to glucocorticoid treatment (>1 mg prednisone-equivalent/kg x 1 week)
Exclusion Criteria:
- Active invasive fungal infection requiring treatment with anti-fungal medication.
- Active viral infection requiring treatment with anti-viral medication.
- Persistence/relapse at the time of study entry of the primary malignancy for which the transplant was performed. Patients with a history of relapsed malignancy who have achieved a remission at the time of evaluation for study participation will not be excluded.
- Known T-cell donor chimerism of <50%.
- Documented DLCO <50% (if performed within 90 days of enrollment) or requirement for supplemental oxygen.
- Pregnancy or breastfeeding. Patients of childbearing capability should agree to use contraception.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1: Infusion of MSCs
First three subjects enrolled will receive a single infusion of mesenchymal stromal cells based on their individual weight
|
Infusion of MSCs delivered to each patient will depend on their weight and assigned dose level.
The maximal individual dose of MSCs any patient will receive is 2 x 1000000 cells/kg.
|
Experimental: Dose Level 2: Infusion of MSCs
Subsequent subjects enrolled will receive two infusions (a week apart) of mesenchymal stromal cells based on their individual weight
|
Infusion of MSCs delivered to each patient will depend on their weight and assigned dose level.
The maximal individual dose of MSCs any patient will receive is 2 x 1000000 cells/kg.
|
Experimental: Dose Level 3: Infusion of MSCs
Subsequent subjects enrolled will receive four infusions (a week apart) of mesenchymal stromal cells based on their individual weight
|
Infusion of MSCs delivered to each patient will depend on their weight and assigned dose level.
The maximal individual dose of MSCs any patient will receive is 2 x 1000000 cells/kg.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of EPIC MSC2014-002 based on dose limiting toxicities (DLTs)
Time Frame: 6 months
|
Number of adverse events that are considered dose limiting toxicities (DLTs).
DLTs will be defined as any grade ≥3 adverse reaction that is unexpected, or considered attributable to the MSC infusion (attribution listed as at least probable).
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate for acute GVHD subjects
Time Frame: 6 months
|
Percentage of subjects that had a complete response (CR) or partial response (PR).
CR is resolution of acute GVHD in all involved organs and PR is improvement of at least 1 stage without worsening in other organ systems.
|
6 months
|
Overall Response Rate for chronic GVHD subjects
Time Frame: 6 months
|
Percentage of subjects that had a reduction in the overall National Institute of Health (NIH) score at three months, without worsening any specific organ.
NIH Criteria for Clinical Trials in Chronic Graft-versus-Host Disease scale: Organs and sites to be scored include skin, mouth, eyes, gastrointestinal tract, liver, lungs, joints and fascia, and the genital tract.
Each organ or site is scored according to a 4-point scale (0 to 3), with 0 representing no involvement and 3 reflecting severe impairment.
Total possible score: 63
|
6 months
|
Transplant-related mortality
Time Frame: 6 months
|
Transplant-related mortality defined as any death occurring in continuous complete remission
|
6 months
|
Incidence of Relapse
Time Frame: 6 months
|
Percentage of subjects who experience relapse of underlying malignancy
|
6 months
|
Disease-free survival
Time Frame: 1 year post transplant
|
Disease-free survival will be defined as survival without relapse of underlying malignancy.
|
1 year post transplant
|
Overall-survival
Time Frame: 1 year post transplant
|
Overall-survival will be defined as survival with or without relapse of underlying malignancy.
|
1 year post transplant
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Muna Qayed, MD, Children's Healthcare of Atlanta/Emory University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00076372
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Graft Versus Host Disease
-
Mesoblast, Inc.Quintiles, Inc.CompletedGrade B Acute Graft Versus Host Disease | Grade C Acute Graft Versus Host Disease | Grade D Acute Graft Versus Host DiseaseUnited States
-
University of LiegeTerminatedChronic Graft-Versus-Host Disease | Acute Graft-Versus-Host Disease | Steroid Refractory Graft-Versus-Host DiseaseBelgium
-
Jazz PharmaceuticalsCompletedAcute-graft-versus-host Disease | Graft-versus-host DiseaseUnited States, Belgium, United Kingdom, Greece, Germany, Spain, France, Italy, Austria, Canada, Bulgaria, Croatia, Poland, Portugal
-
Jonsson Comprehensive Cancer CenterWithdrawnAcute Graft Versus Host Disease | Gastrointestinal Tract Acute Graft Versus Host Disease | Severe Gastrointestinal Tract Acute Graft Versus Host Disease | Steroid Resistant Gastrointestinal Tract Acute Graft Versus Host DiseaseUnited States
-
AltruBio Inc.CompletedSteroid-refractory Acute Graft-versus-Host Disease | Treatment-refractory Acute Graft-versus-Host DiseaseUnited States
-
Shenzhen Xbiome Biotech Co., Ltd.Beijing Improve-Quality Tech.Co., Ltd.Recruiting
-
Cytopeutics Sdn. Bhd.Universiti Tunku Abdul RahmanActive, not recruitingAcute-graft-versus-host DiseaseMalaysia
-
Incyte CorporationTerminatedAcute Graft-versus-host DiseaseUnited States, Spain, France, Italy, United Kingdom, Germany
-
Incyte CorporationCompletedAcute Graft-versus-host DiseaseJapan
-
Central Hospital, Nancy, FranceUnknown
Clinical Trials on Autologous mesenchymal stromal cells (MSCs)
-
Baylor College of MedicineThe Methodist Hospital Research Institute; Center for Cell and Gene Therapy...CompletedCOVID-19 | Acute Respiratory Distress Syndrome | Sars-CoV2United States
-
Federal State Budget Institution Research Center...Not yet recruitingPremature Birth | Neurodevelopmental Disorders | Extreme Prematurity | Preterm Intraventricular Hemorrhage | Hypoxia-Ischemia, CerebralRussian Federation
-
Nationwide Children's HospitalCompletedOsteogenesis Imperfecta Type III | Osteogenesis Imperfecta Type IIUnited States
-
Molly GalloglyNot yet recruitingGraft Versus Host DiseaseUnited States
-
Hospital e Maternidade Dr. Christóvão da GamaIEP São Lucas - Instituto de Ensino e Pesquisa; Clinica Jordy Sinapse; TECHLIFE...CompletedMotor Neuron DiseaseBrazil
-
American CryoStem CorporationTerminatedMultiple SclerosisCayman Islands
-
Emory UniversityNot yet recruitingOsteogenesis Imperfecta | Osteogenesis Imperfecta Type III
-
Mayo ClinicState of Minnesota Regenerative Medicine MinnesotaActive, not recruitingAmyotrophic Lateral Sclerosis | ALSUnited States
-
University College, LondonUnknownTendinopathy | Achilles Tendinitis | Achilles Degeneration | Achilles Tendinitis, Right Leg | Achilles Tendon Thickening | Achilles Tendinitis, Left LegUnited Kingdom
-
Mayo ClinicRegenerative Medicine MinnesotaTerminatedDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type 1 | Diabetic Kidney Disease | Diabetic Nephropathies | Chronic Kidney Disease | Kidney Failure | Diabetic Nephropathy Type 2 | Kidney InsufficiencyUnited States