Biomarkers in Acute Graft-Versus-Host Disease and Extracorporeal Photopheresis Added to Investigator Chosen Therapies of Steroid Refractory Acute GVHD
Condition: Chronic Graft vs. Host Disease; Graft vs Host Disease; Graft-Versus-Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Extracorporeal Photopheresis (ECP); Methoxsalen
Intervention description: 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.; Sterile solution used in conjunction with photopheresis procedure.
Intervention MeSH terms: Methoxsalen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Steroid Failure; Immunomodulation; Corticosteroid Therapy

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  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.

        EXCLUSION CRITERIA:

          -  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.

          -  Inclusion of ECP in the treatment of any patient is contraindicated by any of the
             following:

          -  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