Graft Versus Host DiseasePhase 1NCT02359929
BMT Autologous MSCs for GvHD
A Phase 1 study testing Autologous mesenchymal stromal cells (MSCs) in people with Graft Versus Host Disease and Acute Graft Versus Host Disease, run by Emory University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Graft Versus Host Disease, Acute Graft Versus Host Disease, Chronic Graft Versus Host Disease
- What is being tested?
- Autologous mesenchymal stromal cells (MSCs)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 11 Jan 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta/Emory University
Atlanta, Georgia, 30322
About this study
Official title: 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
Read the 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
- Conditions
- Graft Versus Host Disease, Acute Graft Versus Host Disease, Chronic Graft Versus Host Disease
- Being tested
- Autologous mesenchymal stromal cells (MSCs)
- Keywords
- graft versus host disease, GVHD
- Medical subject headings
- Graft vs Host Disease, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous mesenchymal stromal cells (MSCs)Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1: Infusion of MSCs | Experimental | First three subjects enrolled will receive a single infusion of mesenchymal stromal cells based on their individual weight Receives: Biological: Autologous mesenchymal stromal cells (MSCs) |
| Dose Level 2: Infusion of MSCs | Experimental | Subsequent subjects enrolled will receive two infusions (a week apart) of mesenchymal stromal cells based on their individual weight Receives: Biological: Autologous mesenchymal stromal cells (MSCs) |
| Dose Level 3: Infusion of MSCs | Experimental | Subsequent subjects enrolled will receive four infusions (a week apart) of mesenchymal stromal cells based on their individual weight Receives: Biological: Autologous mesenchymal stromal cells (MSCs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of EPIC MSC2014-002 based on dose limiting toxicities (DLTs)
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).
Measured: 6 months
Secondary outcomes (6)
Overall Response Rate for acute GVHD subjects
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.
Measured: 6 months
Overall Response Rate for chronic GVHD subjects
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
Measured: 6 months
Transplant-related mortality
Transplant-related mortality defined as any death occurring in continuous complete remission
Measured: 6 months
Incidence of Relapse
Percentage of subjects who experience relapse of underlying malignancy
Measured: 6 months
Disease-free survival
Disease-free survival will be defined as survival without relapse of underlying malignancy.
Measured: 1 year post transplant
Overall-survival
Overall-survival will be defined as survival with or without relapse of underlying malignancy.
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startJan 2015
- Primary completion15 Jun 2020
- Study completion11 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- CURE Foundation
- Responsible party
- Principal investigator, Muna Qayed, Emory University
- Investigators
- Muna Qayed, MD, Principal investigator, Children's Healthcare of Atlanta/Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02359929
- Sponsor's protocol ID
- IRB00076372
- Status last verified
- Jan 2023
- First submitted
- 5 Feb 2015
- Last updated
- 12 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Stenger E, Giver CR, Langston A, Kota D, Das PK, Chinnadurai R, Galipeau J, Waller EK, Qayed M. Safety of autologous freshly expanded mesenchymal stromal cells for the treatment of graft-versus-host disease. Front Immunol. 2022 Sep 14;13:959658. doi: 10.3389/fimmu.2022.959658. eCollection 2022.
PubMed 36189324
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Mesenchymal Stromal Cells for the Treatment of Acute and Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT02359929
- Acronym / sponsor ID
- IRB00076372
- Conditions
- Graft Versus Host Disease, Acute Graft Versus Host Disease, Chronic Graft Versus Host Disease
- Keywords
- graft versus host disease, GVHD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- CURE Foundation
- Study start
- Jan 2015 (actual)
- Primary completion
- 15 Jun 2020 (actual)
- Study completion
- 11 Jan 2021 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1: Infusion of MSCs | Experimental | Biological: Autologous mesenchymal stromal cells (MSCs)First three subjects enrolled will receive a single infusion of mesenchymal stromal cells based on their individual weight |
| Dose Level 2: Infusion of MSCs | Experimental | Biological: Autologous mesenchymal stromal cells (MSCs)Subsequent subjects enrolled will receive two infusions (a week apart) of mesenchymal stromal cells based on their individual weight |
| Dose Level 3: Infusion of MSCs | Experimental | Biological: Autologous mesenchymal stromal cells (MSCs)Subsequent subjects enrolled will receive four infusions (a week apart) of mesenchymal stromal cells based on their individual weight |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous mesenchymal stromal cells (MSCs)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. | Biological | Dose Level 1: Infusion of MSCs, Dose Level 2: Infusion of MSCs, Dose Level 3: Infusion of MSCs |
Primary outcome
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 secondary outcomes
Overall Response Rate for acute GVHD subjects
Time frame: 6 months
Overall Response Rate for chronic GVHD subjects
Time frame: 6 months
Transplant-related mortality
Time frame: 6 months
Incidence of Relapse
Time frame: 6 months
Disease-free survival
Time frame: 1 year post transplant
Overall-survival
Time frame: 1 year post transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
- Results publication: PubMed 36189324Stenger E, Giver CR, Langston A, Kota D, Das PK, Chinnadurai R, Galipeau J, Waller EK, Qayed M. Safety of autologous freshly expanded mesenchymal stromal cells for the treatment of graft-versus-host disease. Front Immunol. 2022 Sep 14;13:959658. doi: 10.3389/fimmu.2022.959658. eCollection 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muna Qayed, MD principal investigator
Children's Healthcare of Atlanta/Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous mesenchymal stromal cells (MSCs) in people with Graft Versus Host Disease and Acute Graft Versus Host Disease, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of EPIC MSC2014-002 based on dose limiting toxicities (DLTs) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02359929, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2023.