Graft Versus Host DiseasePhase 2NCT05333029
Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for GVHD
A Phase 2 study testing Allogeneic mesenchymal stromal cells (MSCs) and Extracorporeal photopheresis (ECP) in people with Graft Versus Host Disease, run by Molly Gallogly at 1 site in United States.
Trial summary
The purpose of this study is to see if two treatments (extracorporeal photopheresis and Mesenchymal Stromal Cell (MSC) infusion, can be given safely together, and if they improve the symptoms of a Graft versus Host Disease (GvHD), a complication that can occur in people who undergo stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Allogeneic mesenchymal stromal cells (MSCs) and Extracorporeal photopheresis (ECP)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2024to 1 Jun 2025
- Phase
- Phase 2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -One of the following diagnoses:
- --High risk aGVHD, either biopsy proven or clinical diagnosed as defined by either:
- Skin stage 4
- Lower gastrointestinal (GI) stage ≥ 3
- Liver stage ≥ 3
- Skin stage 3 and lower GI or liver stage ≥ 2 GVHD
Show all 18Show fewer
- Hyper-acute GVHD as defined by aGVHD within the first 14 days of transplant
- Overall grade 2-4 aGVHD with high-risk disease identified by the Viracor Eurofins Symptomatic Onset or Post-Treatment Algorithm
- OR:
- --Steroid refractory aGVHD (either biopsy proven or clinical diagnosed) as defined by any one of the following criteria per NCCN (National Comprehensive Cancer Network) Guidelines for Hematopoietic Cell Transplantation (HCT):
- Progression of aGVHD within 3-5 days of therapy onset with ≥ 2 mg/kg/day of methylprednisolone or equivalent
- Failure to improve within 5-7 days of treatment initiation (2 mg/kg/day of methylprednisolone or equivalent)
- Incomplete response after more than 28 days of immunosuppressive treatment including steroids (2 mg/kg/day of methylprednisolone or equivalent)
- Hct > 27 and plts > 50,000 x10^9/L (may be achieved via transfusion on ECP days)
- Candidate for appropriate vascular access for ECP, which may include: (1) peripheral IV with 16 or 17 gauge Fistula needle; (2) central venous access device (apheresis catheter, tunneled central vascular access device), (3) vortex implanted port; (4) Bard POWERFLOW® implanted port
- Eastern Cooperative Oncology Group Performance status ≤ 3
- Participants who underwent an allogeneic hematopoietic stem cell transplantation from any donor source
- Participants must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Active malignancy
- Contraindication to photopheresis, including any of the following: (1) known sensitivity to psoralen compounds such as 8-MOP; (2) comorbidities that may result in photosensitivity; (3) aphakia; (4) insufficient weight/circulating volume (defined by photopheresis machine characteristics); (5) hemodynamic instability; (6) platelet count < 20 x 109/μL despite platelet support; (7) bleeding diathesis; (8) hematocrit < 27 despite red blood cell support; (9) inability to lie flat for 4 hours; (10) inadequate venous access
- Participants with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC (Reduced-Intensity Conditioning) have the significant potential for teratogenic or abortifacient effects.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
- Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
- Progressive underlying malignant disease or post-transplant lymphoproliferative disease
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
About this study
Official title: A Phase II Study of Combination Treatment with Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for High-Risk and Steroid-Refractory Acute GVHD
The purpose of this study is to see if two treatments (extracorporeal photopheresis and Mesenchymal Stromal Cell (MSC) infusion, can be given safely together, and if they improve the symptoms of a Graft versus Host Disease (GvHD), a complication that can occur in people who undergo stem cell transplant.
Read the detailed description
This is a Phase II study of human MSCs for the treatment of High-Risk aGVHD (HRaGVHD) and steroid-refractory acute GVHD (SRaGVHD). MSCs are cells that can help the body heal from injury and maintain a healthy immune system. MSCs have been used to prevent and treat a GvHD. In previous human studies, MSC infusion has been generally well-tolerated and safe, and in some cases, benefit was reported. The donor of the MSCs could be a relative or a stranger, and does not need to be the same individual who donated the stem cells for the stem cell transplant. All donors are screened for infectious diseases, similar to a blood donor. All donors have a physical exam.
Corticosteroids may be administered with MSCs/ECP. Continued use of anti-infective medications, GVHD prophylaxis medications (including calcineurin inhibitors), transfusion support, and topical steroid therapy is permitted. Participants will be assessed for safety and tolerability using a continuous monitoring approach. In order to be included in the tolerability review, participants must have received at least 1 treatment with MSCs.
- Conditions
- Graft Versus Host Disease
- Being tested
- Allogeneic mesenchymal stromal cells (MSCs), Extracorporeal photopheresis (ECP)
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic mesenchymal stromal cells (MSCs)Biological
Treatment dose 2 x10^6 cells/kg (+/- 20%)
Extracorporeal photopheresis (ECP)Biological
Blood is collected through an intravenous (IV) line which is connected to an apheresis machine.The machine adds a chemical that makes the white blood cells sensitive to light. Then the machine shines a light on the cells and then returns the blood to the participant
| Study group | Role | What they receive |
|---|---|---|
| MSCs + ECP | Experimental | The treatment period consists of a single, 28-day cycle. Participants will be treated with ECP 2 to 3 times per week per the discretion of the treating physician. Participants will receive IV infusions of MSCs on days 1 (+ 2 days) and 8 (+/- 2 days). A third dose may be given on day 15 (+/- 2 days) if the principal investigator (PI) and treating physician determine the MSC infusions have benefited the participant.
Participants will be followed for up to 1 year for assessment of endpoints. Receives: Biological: Allogeneic mesenchymal stromal cells (MSCs); Biological: Extracorporeal photopheresis (ECP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of participants with response to therapy
Response to therapy:
Complete Remission (CR): Defined as the complete resolution of aGVHD symptoms in all organs, without secondary GVHD therapy.
Partial Remission (PR): Defined as improvement in GVHD stage in all initial GVHD target organs without complete resolution and without worsening in any other GVHD target organs, without secondary GVHD therapy.
The true response rate will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method
Measured: Day 28
Secondary outcomes (14)
aGVHD severity per Blood and Marrow Transplant Clinical Trials Network Manual of Operations (BMT MOP).
Acute GVHD Staging per BMT MOP
Stage 1:
- Skin: Maculopapular Rash < 25% body surface area (BSA)
- Gastrointestinal (GI): Diarrhea < 500 mL/day or persistent nausea
- Liver: Total bilirubin 2.1-3 mg/dL
Stage 2:
- Skin: Maculopapular Rash 25-50% BSA
- Gastrointestinal (GI): Diarrhea > 500 mL/day
- Liver: Total bilirubin 3.1-6 mg/dL
Stage 3:
- Skin: Maculopapular Rash > 50% BSA
- Gastrointestinal (GI): Diarrhea > 1000 mL/day
- Liver: Total bilirubin 6.1-15 mg/dL
Stage 4:
- Skin: Generalized erythroderma with bullae
- Gastrointestinal (GI): Diarrhea > 1500 mL/day
- Liver: Total bilirubin >15 mg/dL
Measured: 100 days post-intervention
aGVHD incidence
the number of participants that had acute GVHD incidence
Measured: 100 days post-intervention
Safety as measured by number of adverse events attributed to MSC and ECP therapy
To evaluate the total number of adverse events attributed to MSC and ECP therapy
Measured: Day 30
Safety as measured by severity of adverse events attributed to MSC and ECP therapy
number of participants with adverse events (above or equal to grade 3) attributed to MSC and ECP therapy
Measured: Day 30
Number of participants with non-relapse mortality (NRM)
Measured: 1 year
Number of participants with relapse-related mortality
Measured: 1 year
Average time to relapse
Average time to relapse. The Kaplan-Meier method will be used to estimate survivor function
Measured: 1 year
Chronic GVHD incidence
the number of participants that had Chronic GVHD incidence
Measured: At 1 year from the start of treatment
Overall Survival (OS)
Average OS. The Kaplan-Meier method will be used to estimate survivor function
Measured: 1 year
Steroid dose decrease
change in steroid dose from day 1 to day 28
Measured: Up to day 28
Steroid discontinuation rate
Percentage of patients who are no longer taking systemic corticosteroids at day 28
Measured: Up to day 28
Change in FACT-BMT (Functional Assesment of Cancer Therapy-Bone Marrow Transplant) survey score
Quality of life survey scores measured by change in FACT-BMT survey scores. The Functional Assessment of Cancer Therapy-General (FACT-G) subscales, total score on their 12-item BMT subscale including physical, social, emotional and functional well-being measured over time will be summarized by mean and standard deviation at each time point.
The QOL data will be further analyzed using repeated measures regression models, i.e., mixed-effects models 28-30 ,28-30 with an unstructured covariance matrix and a categorical effect of time to calculate between-group differences in improvement from baseline in these QOL outcomes
Measured: 1 year
Percent regulatory T cells (% Tregs)
T cell subsets in responders vs. nonresponders as measured by percent Tregs
Measured: Up to 1 year after treatment
CD4:CD8 ratio
T cell subsets in responders vs. nonresponders as measured by cluster of differentiation (CD)4:CD8 ratio
Measured: Up to 1 year after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2022
- Study start1 Oct 2024 (estimated)
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Jun 2025 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Molly Gallogly
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Molly Gallogly, Case Comprehensive Cancer Center
- Investigators
- Molly Gallogly, MD, PhD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05333029
- Sponsor's protocol ID
- CASE1Z20
- Status last verified
- Nov 2024
- First submitted
- 4 Apr 2022
- Last updated
- 7 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) that underlie or influence the results observed from the study
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Combination Treatment with Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for High-Risk and Steroid-Refractory Acute GVHD
- ClinicalTrials.gov ID
- NCT05333029
- Acronym / sponsor ID
- CASE1Z20
- Conditions
- Graft Versus Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Molly GalloglyUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 18 Apr 2022 (actual)
- 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.
The purpose of this study is to see if two treatments (extracorporeal photopheresis and Mesenchymal Stromal Cell (MSC) infusion, can be given safely together, and if they improve the symptoms of a Graft versus Host Disease (GvHD), a complication that can occur in people who undergo stem cell transplant.
Detailed description
This is a Phase II study of human MSCs for the treatment of High-Risk aGVHD (HRaGVHD) and steroid-refractory acute GVHD (SRaGVHD). MSCs are cells that can help the body heal from injury and maintain a healthy immune system. MSCs have been used to prevent and treat a GvHD. In previous human studies, MSC infusion has been generally well-tolerated and safe, and in some cases, benefit was reported. The donor of the MSCs could be a relative or a stranger, and does not need to be the same individual who donated the stem cells for the stem cell transplant. All donors are screened for infectious diseases, similar to a blood donor. All donors have a physical exam.
Corticosteroids may be administered with MSCs/ECP. Continued use of anti-infective medications, GVHD prophylaxis medications (including calcineurin inhibitors), transfusion support, and topical steroid therapy is permitted. Participants will be assessed for safety and tolerability using a continuous monitoring approach. In order to be included in the tolerability review, participants must have received at least 1 treatment with MSCs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MSCs + ECP | Experimental | Biological: Allogeneic mesenchymal stromal cells (MSCs), Biological: Extracorporeal photopheresis (ECP)The treatment period consists of a single, 28-day cycle. Participants will be treated with ECP 2 to 3 times per week per the discretion of the treating physician. Participants will receive IV infusions of MSCs on days 1 (+ 2 days) and 8 (+/- 2 days). A third dose may be given on day 15 (+/- 2 days) if the principal investigator (PI) and treating physician determine the MSC infusions have benefited the participant. Participants will be followed for up to 1 year for assessment of endpoints. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Skin stage 4
- Lower gastrointestinal (GI) stage ≥ 3
- Liver stage ≥ 3
- Skin stage 3 and lower GI or liver stage ≥ 2 GVHD
- Hyper-acute GVHD as defined by aGVHD within the first 14 days of transplant
Key exclusion criteria (7 listed)
- Active malignancy
- Contraindication to photopheresis, including any of the following: (1) known sensitivity to psoralen compounds such as 8-MOP; (2) comorbidities that may result in photosensitivity; (3) aphakia; (4) insufficient weight/circulating volume (defined by photopheresis machine characteristics); (5) hemodynamic instability; (6) platelet count < 20 x 109/μL despite platelet support; (7) bleeding diathesis; (8) hematocrit < 27 despite red blood cell support; (9) inability to lie flat for 4 hours; (10) inadequate venous access
- Participants with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC (Reduced-Intensity Conditioning) have the significant potential for teratogenic or abortifacient effects.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
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 |
|---|---|---|
| Allogeneic mesenchymal stromal cells (MSCs)Treatment dose 2 x10^6 cells/kg (+/- 20%) | Biological | MSCs + ECP |
| Extracorporeal photopheresis (ECP)Blood is collected through an intravenous (IV) line which is connected to an apheresis machine.The machine adds a chemical that makes the white blood cells sensitive to light. Then the machine shines a light on the cells and then returns the blood to the participant | Biological | MSCs + ECP |
Primary outcome
Percent of participants with response to therapy
Time frame: Day 28
Response to therapy: Complete Remission (CR): Defined as the complete resolution of aGVHD symptoms in all organs, without secondary GVHD therapy. Partial Remission (PR): Defined as improvement in GVHD stage in all initial GVHD target organs without complete resolution and without worsening in any other GVHD target organs, without secondary GVHD therapy. The true response rate will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method
14 secondary outcomes
aGVHD severity per Blood and Marrow Transplant Clinical Trials Network Manual of Operations (BMT MOP).
Time frame: 100 days post-intervention
aGVHD incidence
Time frame: 100 days post-intervention
Safety as measured by number of adverse events attributed to MSC and ECP therapy
Time frame: Day 30
Safety as measured by severity of adverse events attributed to MSC and ECP therapy
Time frame: Day 30
Number of participants with non-relapse mortality (NRM)
Time frame: 1 year
Number of participants with relapse-related mortality
Time frame: 1 year
Average time to relapse
Time frame: 1 year
Chronic GVHD incidence
Time frame: At 1 year from the start of treatment
Overall Survival (OS)
Time frame: 1 year
Steroid dose decrease
Time frame: Up to day 28
Steroid discontinuation rate
Time frame: Up to day 28
Change in FACT-BMT (Functional Assesment of Cancer Therapy-Bone Marrow Transplant) survey score
Time frame: 1 year
Percent regulatory T cells (% Tregs)
Time frame: Up to 1 year after treatment
CD4:CD8 ratio
Time frame: Up to 1 year after treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) that underlie or influence the results observed from the study
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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.
Molly Gallogly, MD, PhD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic mesenchymal stromal cells (MSCs) and Extracorporeal photopheresis (ECP) in people with Graft Versus Host Disease, run by Molly Gallogly 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 18 inclusion and 7 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: withdrawn, as of the sponsor's last update on 7 Jan 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Percent of participants with response to therapy (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jan 2025.