Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for GVHD

NCT05333029 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CASE1Z20
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• aGVHD severity per Blood and Marrow Transplant Clinical Trials Network Manual of Operations (BMT MOP).

  100 days post-intervention

• aGVHD incidence

  100 days post-intervention

• Safety as measured by number of adverse events attributed to MSC and ECP therapy

  Day 30

• Safety as measured by severity of adverse events attributed to MSC and ECP therapy

  Day 30

• Number of participants with non-relapse mortality (NRM)

  1 year

Study Arms (1)

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.

Biological: Allogeneic mesenchymal stromal cells (MSCs); Biological: Extracorporeal photopheresis (ECP)

Interventions

Allogeneic mesenchymal stromal cells (MSCs) BIOLOGICAL

Treatment dose 2 x10\^6 cells/kg (+/- 20%)

MSCs + ECP

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

MSCs + ECP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Molly Gallogly: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Photopheresis

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Molly Gallogly, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 18, 2022
• Study Start: October 1, 2024
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: January 7, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data

Locations

US (1)