Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for GVHD

Graft Versus Host Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05333029
• Other study ID #: CASE1Z20
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: June 1, 2025

Study information

• Verified date: November 2023
• Source: Case Comprehensive Cancer Center
• Contact: Molly Gallogly, MD, PhD
• Phone: 1-800-641-2422
• Email: CTUReferral[@]UHhospitals.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: June 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

-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
• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Biological:
• Allogeneic mesenchymal stromal cells (MSCs)
Treatment dose 2 x10^6 cells/kg (+/- 20%)
• 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

Locations

Country	Name	City	State
United States	University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Molly Gallogly

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 28
Secondary	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	100 days post-intervention
Secondary	aGVHD incidence	the number of participants that had acute GVHD incidence	100 days post-intervention
Secondary	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	Day 30
Secondary	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	Day 30
Secondary	Number of participants with non-relapse mortality (NRM)		1 year
Secondary	Number of participants with relapse-related mortality		1 year
Secondary	Average time to relapse	Average time to relapse. The Kaplan-Meier method will be used to estimate survivor function	1 year
Secondary	Chronic GVHD incidence	the number of participants that had Chronic GVHD incidence	At 1 year from the start of treatment
Secondary	Overall Survival (OS)	Average OS. The Kaplan-Meier method will be used to estimate survivor function	1 year
Secondary	Steroid dose decrease	change in steroid dose from day 1 to day 28	Up to day 28
Secondary	Steroid discontinuation rate	Percentage of patients who are no longer taking systemic corticosteroids at day 28	Up to day 28
Secondary	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	1 year
Secondary	Percent regulatory T cells (% Tregs)	T cell subsets in responders vs. nonresponders as measured by percent Tregs	Up to 1 year after treatment
Secondary	CD4:CD8 ratio	T cell subsets in responders vs. nonresponders as measured by cluster of differentiation (CD)4:CD8 ratio	Up to 1 year after treatment