Clinical trial NCT05333029: Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for GVHD
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Graft Versus Host Disease
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2022-04-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent of participants with response to therapy
timeFrame: Day 28
Secondary outcomes:
measure: aGVHD severity per Blood and Marrow Transplant Clinical Trials Network Manual of Operations (BMT MOP).
timeFrame: 100 days post-intervention
measure: aGVHD incidence
timeFrame: 100 days post-intervention
measure: Safety as measured by number of adverse events attributed to MSC and ECP therapy
timeFrame: Day 30
measure: Safety as measured by severity of adverse events attributed to MSC and ECP therapy
timeFrame: Day 30
measure: Number of participants with non-relapse mortality (NRM)
timeFrame: 1 year
measure: Number of participants with relapse-related mortality
timeFrame: 1 year
measure: Average time to relapse
timeFrame: 1 year
measure: Chronic GVHD incidence
timeFrame: At 1 year from the start of treatment
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Steroid dose decrease
timeFrame: Up to day 28
measure: Steroid discontinuation rate
timeFrame: Up to day 28
measure: Change in FACT-BMT (Functional Assesment of Cancer Therapy-Bone Marrow Transplant) survey score
timeFrame: 1 year
measure: Percent regulatory T cells (% Tregs)
timeFrame: Up to 1 year after treatment
measure: CD4:CD8 ratio
timeFrame: Up to 1 year after treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Molly Gallogly, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: