Clinical Trial: A Safety and Efficacy Study of Uvadex and Extracorporeal Photopheresis (ECP) in Chronic Graft Versus Host Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy With UVADEX for the Treatment of Patients With Moderate to Severe Chronic Graft-versus-Host Disease

Brief Summary: The purpose of this study is to evaluate the safety and effectiveness of extracorporeal photopheresis therapy when added to standard drug therapies administered to patients with moderate to severe chronic graft-versus-host disease.

Detailed Summary: This is an open-label study (patients and study staff will know the identity of treatments assigned during the study) in patients with chronic graft-versus-host disease (cGvHD). Chronic graft-versus-host disease (a donator-versus-recipient-disease) is a complication that can occur after a blood stem cell or bone marrow transplant with cells from a related or unrelated donator. During cGvHD, the transplanted cells attack the recipient's body. Patients with cGVHD who meet entry criteria for the study will be randomly assigned to receive standard of care treatment for 26 weeks or standard or care treatment with extracorporeal photopheresis (ECP) for 26 weeks. Standard of care treatment consists of orally (taken by mouth) administered corticosteroids (drugs that reduce inflammation) and cyclosporine (CsA)or Tacrolimus ( drugs that suppress the patient's immune response). ECP therapy is a process that takes place in a device where the investigational drug UVADEX (methoxsalen) is injected into a germ-free bag mixed with the patient's white blood cells. After the blood cells have absorbed the drug and are exposed to ultraviolet A (UVA) radiation, the blood cells are injected back into the patient's body. During the study, a third party assessor at each study center who will be blinded (will not know) to treatment will assess the condition each patient's skin and oral mucosa at protocol-specified visits and will complete a total skin score for all patients . The study will consist of 3 phases: a screening phase, an open label treatment phase and an end-of-study (or early withdrawal) phase. The duration of patient participation will be 28 weeks and patient safety will be monitored throughout the study. An additional non-interventional 2 year follow-up will begin after the 28 week/withdrawal end-of-study phase.
Sponsor: Mallinckrodt

Current Primary Outcome:

• Overall response (complete or partial response) in cGvHD according to NIH Response Criteria [ Time Frame: week 28 ]
  The NIH Consensus grading and severity criteria includes physical assessments of skin,oral cavity,eyes,gynecological and laboratory data and patient reports.Each domain is scored from 0 (no involvement) to 3 (severe involvement)
• Overall survival (long term follow up) [ Time Frame: 12 and 24 months ]
  Comparison of overall survival for Standard of Care (SOC) arm vs SOC+ECP

Original Primary Outcome: Overall response (complete or partial response) in cGvHD according to NIH Response Criteria [ Time Frame: week 28 ]

Current Secondary Outcome:

• Proportion of patients in each treatment group achieving response rates (complete or partial) by organ system involvement [ Time Frame: Change from baseline to week 28 ]
  Each organ system will be assessed through the use of NIH Consensus Criteria
• Correlation between total skin score and skin assessment (% of skin involvement) [ Time Frame: up to week 28 ]
  Performed by using NIH Consensus Criteria Clinical Assessment
• Quality of Life (QoL) Questionnaire SF 36 short version scores [ Time Frame: change in baseline to week 28 ]
  The SF36 (Short Form with 36 questions) is a self-administered QoL scoring system that includes eight independent scales and two main dimensions and its scales and dimensions, scored as a number between 0 and 100 with a higher score indicating better functioning.
• QoL questionnaire, Bone marrow Transplant scores [ Time Frame: change from baseline to week 28 ]
  The Functional Assessment of Cancer and Bone Marrow Transplant (FACT-BMT) is a self-administered instrument that consists of the 27-item General and the 23-item Bone Marrow Transplantation Subscales; each item is scored on a 5-point response scale ranging from 0 to 4 (0=not at all to 4=very much).
• Relapse of underlying malignancy [ Time Frame: up to week 28 ]
  relapse as confirmed by physician
• Results from clinical laboratory tests [ Time Frame: up to week 28 ]
  Clinical laboratory tests includes hematology and chemistry parameters
• Adverse Events Reported [ Time Frame: up to week 28 ]
• Failure free survival [ Time Frame: 12 and 24 months ]
  Compare 12 month and 24 month failure free survival from time of last visit in primary study. Failure free survival defined as lack of recurrence of GvHD, lack of addition of new immunosuppressive therapy, lack of relapse, and lack of death from any cause
• Relapse rates of underlying malignancy [ Time Frame: 12 and 24 months ]
  Compare the relapse rates of underlying malignancy in the SOC arm vs the SOC+ECP arm from the primary study
• Status and severity of cGvHD [ Time Frame: 12 and 24 months ]
  Compare status and severity of cGvHD in the overall patient and individual organ systems involved of the SOC arm vs the SOC+ECP arm from the primary study
• SAEs due to hospitalization [ Time Frame: 12 and 24 months ]
  Compare the SAEs due to hospitalization in the SOC arm vs the SOC+ECP arm from the primary study
• Overall survival (SOC vs SOC+ECP) [ Time Frame: 12 and 24 months ]
  Assess overall survival of patients receiving SOC+ECP after the primary study vs patients not receiving ECP
• cGvHD status and severity (SOC vs SOC+ECP) [ Time Frame: 12 and 24 months ]
  Assess cGvHD status and severity in patients receiving SOC+ECP after the primary study vs patients not receiving ECP
• Overall survival (ECP vs no ECP) [ Time Frame: 12 and 24 months ]
  Assess overall survival of SOC+ECP arm who continue ECP treatment after primary study vs SOC+ECP arm patients who discontinue ECP treatment after primary study
• cGvHD status and severity (ECP vs no ECP) [ Time Frame: 12 and 24 months ]
  Assess cGvHD status and severity in SOC+ECP arm who continue ECP treatment after primary study vs SOC+ECP arm patients who discontinue ECP treatment after primary study

Original Secondary Outcome:

• Proportion of patients in each treatment group achieving response rates (complete or partial) by organ system involvement [ Time Frame: Change from baseline to week 28 ]
  Each organ system will be assessed through the use of NIH Consensus Criteria
• Correlation between total skin score and skin assessment (% of skin involvement) [ Time Frame: up to week 28 ]
  Performed by using NIH Consensus Criteria Clinical Assessment
• Quality of Life (QoL) Questionnaire SF 36 short version scores [ Time Frame: change in baseline to week 28 ]
  The SF36 (Short Form with 36 questions) is a self-administered QoL scoring system that includes eight independent scales and two main dimensions and its scales and dimensions, scored as a number between 0 and 100 with a higher score indicating better functioning.
• QoL questionnaire, Bone marrow Transplant scores [ Time Frame: change from baseline to week 28 ]
  The Functional Assessment of Cancer and Bone Marrow Transplant (FACT-BMT) is a self-administered instrument that consists of the 27-item General and the 23-item Bone Marrow Transplantation Subscales; each item is scored on a 5-point response scale ranging from 0 to 4 (0=not at all to 4=very much).
• Relapse of underlying malignancy [ Time Frame: up to week 28 ]
  relapse as confirmed by physician
• Results from clinical laboratory tests [ Time Frame: up to week 28 ]
  Clinical laboratory tests includes hematology and chemistry parameters
• Adverse Events Reported [ Time Frame: up to week 28 ]

Information By: Mallinckrodt

Dates:
Date Received: June 22, 2011
Date Started: November 2011
Date Completion:
Last Updated: May 17, 2017
Last Verified: May 2017