Biomarkers in Acute Graft-Versus-Host Disease and Extracorporeal Photopheresis Added to Investigator Chosen Therapies of Steroid Refractory Acute GVHD

NCT02322190 | Terminated Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 15003915-C-0039
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Some allogeneic stem cell transplant recipients get acute graft-versus-host disease (GVHD). They always get steroids as the first treatment, but this may not work. Those people where steroids are not enough may benefit from a treatment called extracorporeal photopheresis (ECP). ECP exposes white blood cells to ultraviolet light outside the body. Researchers want to study how certain markers in the blood predict the severity and outcome of acute GVHD and how ECP treatments work for people with acute GVHD. They will also study how these markers in the blood may help predict who should get ECP and its effects on the immune system. Objectives: \- To learn more about treatments for acute GVHD after allogeneic stem cell transplantation. Eligibility: \- Adults with acute GVHD enrolled in an National Cancer Institute (NCI) allogeneic transplantation protocol. Design:

• Transplant physicians will confirm participant eligibility.
• Participants will receive treatment with steroids for their acute GVHD as prescribed by their transplant physician. This will continue while they are enrolled on this study.
• If steroids work in treating their acute GVHD, then every 28 days for 6 months, participants will have:
• a physical exam.
• blood tests.
• If steroids do not work, participants will get additional treatments as prescribed by their transplant physician who may choose to use ECP as a part of this additional treatment. For ECP, blood is removed through an intravenous (IV) catheter. A machine separates the white blood cells from the other blood parts. Those cells are treated with methoxsalen and exposed to ultraviolet light. Then they are returned to the participant through their IV.
• Participants who get ECP will over at least 6 months have:
• veins researched. They may have a catheter placed in a larger vein in the chest or groin.
• multiple blood tests.
• multiple pregnancy tests (if needed).
• multiple ECP procedures.
• At the end of ECP treatment and 6 months after ECP, participants will have additional physical exams and blood tests.

Conditions

Chronic Graft vs. Host Disease; Graft vs Host Disease; Graft-Versus-Host Disease

Keywords

Steroid Failure; Immunomodulation; Corticosteroid Therapy

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Biomarkers (Serum TIM3, IL-6, Reg-3-a, ST2, LPS-BP, Nitrate, TNFR1, IL-2Ra, CXCL10, and HGF) Present in Blood and/or Tissue Who Were Steroid Refractory After ECP Treatment

  In an effort to determine steroid refractoriness after Extracorporeal Photopheresis (ECP) treatment, tissue and blood obtained from participants was examined to see if biomarkers (i.e., Serum T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), ST2, Nitrate, Interleukin-6 (IL-6), regenerating family member 3 alpha (Reg-3-a), lipopolysaccharide binging protein (LPS-BP), tumor necrosis factor receptor 1 (TNFR1), interleukin-2 receptor alpha chain (IL-2Ra), CXC motif chemokine 10 (CXCL10), hepatocyte growth factor (HGF)) were present.

  14 Days

• Number of Participants With Steroid Refractory Disease Who Had Improvement and/or Resolution of Graft-versus-host Disease (GVHD) Associated Symptoms

  GVHD associated symptoms was assessed by the American Society for Bone Marrow Transplantation consensus statement. Complete Response (CR) is no residual organ specific symptoms or findings. Very Good Partial Response (VGPR) is Skin: An active erythematous rash involving \< 25% of the body surface area; Liver: Persistent low-level hyperbilirubinemia, and/or Gut: Gastrointestinal function and water resorption in the colon are approaching normal. Partial Response (PR) is any improvement over baseline symptoms. Progressive disease (PD) is stable or worsening organ specific findings requiring change of therapy.

  7 months

Secondary Outcomes (2)

• Days to Overall Survival

  time from study entry to end of observations/off study, up to a year

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

  Date treatment consent signed to date off study, approximately 8 months and 6 days

Study Arms (2)

Investigator chosen second line therapy

NO INTERVENTION

Investigator chosen second line therapy

Second line therapy + Extracorporeal Photopheresis

EXPERIMENTAL

Second line therapy in addition to Extracorporeal Photopheresis (ECP)

Procedure: Extracorporeal Photopheresis (ECP); Drug: Methoxsalen

Interventions

Extracorporeal Photopheresis (ECP) PROCEDURE

Twice weekly for 1 month or Twice every other week for 2 months or Twice during one week per month for 4 months for a total of up to 7 months of treatment.

Also known as: Extracorporeal Photopheresis

Second line therapy + Extracorporeal Photopheresis

Methoxsalen DRUG

Sterile solution used in conjunction with photopheresis procedure.

Also known as: Oxsoralen-Ultra

Second line therapy + Extracorporeal Photopheresis

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to18 years.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Subject must be also enrolled on an National Cancer Institute (NCI) allogeneic transplant protocol.
• Patients must agree to practice effective contraception (both male and female subjects, if the risk of conception exists)The effects of Extracorporeal Photopheresis (ECP) on the developing human fetus are unknown. For this reason and as well as other Methoxsalen used in this trial is in a class of agents that is known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 4 months after the completion of study treatment. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Any physical or mental condition that, in the opinion of the principal Investigator (PI), would cause the risk/benefit ratio of participation to be unacceptable.
• Unstable hemodynamics requiring vasopressors or other support measures not amenable to or medically appropriate for continuation during the procedure.
• Uncontrolled infection.
• Inability to maintain acceptable venous access.
• Uncontrolled or uncorrectable coagulopathy.
• Pregnant women are excluded from ECP because methoxsalen, an agent utilized for the study procedure, may cause fetal harm. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with methoxsalen, breastfeeding should be discontinued if the mother is treated with methoxsalen. Pregnancy will be evaluated prior to initiation of ECP.
• History of allergic or idiosyncratic/hypersensitivity reactions to 8- methoxypsoralen/psoralen compounds.
• History of a light-sensitive cutaneous disease
• Subjects with aphakia

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Photopheresis; Methoxsalen

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Ronald Gress
• Organization: National Cancer Institute

rg26g@nih.gov

240-760-6167

Study Officials

• Ronald E Gress, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2014
• First Posted: December 23, 2014
• Study Start: December 20, 2014
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)