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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: June 22, 2011
Last updated: September 2, 2014
Last verified: September 2014
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.

Condition Intervention Phase
Chronic Graft Versus Host Disease
Drug: ECP(Methoxsalen)+Corticosteroids+Cyclosporine or Tacrolimus
Drug: Corticosteroids/Cyclosporine/Tacrolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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 (cGvHD)

Resource links provided by NLM:

Further study details as provided by Mallinckrodt:

Primary Outcome Measures:
  • Overall response (complete or partial response) in cGvHD according to NIH Response Criteria [ Time Frame: week 28 ] [ Designated as safety issue: No ]
    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)

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    relapse as confirmed by physician

  • Results from clinical laboratory tests [ Time Frame: up to week 28 ] [ Designated as safety issue: No ]
    Clinical laboratory tests includes hematology and chemistry parameters

  • Adverse Events Reported [ Time Frame: up to week 28 ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: November 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ECP+Corticosteroids+Cyclosporine or Tacrolimus
ECP UVADEX dose (TBD) administered during Wks 2-10 (2x/wk), Wks 11-18 (2x/wk every 2 wks), and Wks 19-26 (2x/wk every 4 wks) along with corticosteroids at a dose of 1.0 mg/kg prednisone, or equivalent, daily, tapered to 0.125 mg/kg daily by Wk 24 and maintained at that dose until Wk 28.
Drug: ECP(Methoxsalen)+Corticosteroids+Cyclosporine or Tacrolimus
ECP UVADEX dose (TBD) administered during Wks 2-10 (2x/wk), Wks 11-18 (2x/wk every 2 wks), and Wks 19-26 (2x/wk every 4 wks) along with corticosteroids at a dose of 1.0 mg/kg prednisone, or equivalent, daily, tapered to 0.125 mg/kg daily by Wk 24 and maintained at that dose until Wk 28.
Other Names:
  • Uvadex
  • ECP
Active Comparator: Corticosteroids/Cyclosporine/Tacrolimus
1.0 mg/kg prednisone, or equivalent, daily, tapered to 0.125 mg/kg daily by Wk 24 and maintained at that dose until Wk 28 administered with cyclosporine or Tacrolimus (dose of cyclosporine and Tacrolimus should be consistent with local institutional practice).
Drug: Corticosteroids/Cyclosporine/Tacrolimus
1.0 mg/kg prednisone, or equivalent, daily, tapered to 0.125 mg/kg daily by Wk 24 and maintained at that dose until Wk 28 administered with cyclosporine or Tacrolimus (dose of cyclosporine/Tacrolimus should be consistent with local institutional practice).

Detailed Description:
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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Have new onset of moderate or severe cGvHD as assessed by the NIH Consensus Criteria Clinical Assessment (staging and severity) with onset within 2 years of transplantation (Patients with prior acute GvHD should be on a stable dose of <0.5 mg/kg daily prednisone, or equivalent, for at least 2 weeks prior to study entry. Prior ECP for patients with acute GvHD is permitted in the study);willing to start 1.0mg/kg prednisone: Be using adequate birth control; If a woman, must have negative pregnancy test result at screening: Be able and willing to comply with all study procedures including providing informed consent

Exclusion Criteria:

  • Be intolerant to corticosteroids; Received treatment with >2.0 mg daily prednisone, or equivalent, for cGvHD for more than 7 days prior to baseline visit; received treatment with prednisone for mild cGVHD with >.5mg/kg for > 14 days, Have evidence of known infection with human immunodeficiency virus (HIV), active Hepatitis B infection, or have uncontrolled infection requiring treatment at the time of study entry; Requires treatment with budesonide and similar low absorption oral steroids and steroid enema preparations; Receiving treatment with mycophenolate mofetil (MMF),PUVA, tyrosine kinase inhibitors, anti-tumor necrosis factor (TNF) agents, sirolimus, and bortezomib; Receiving treatment with alemtuzumab, antithymocyte globulin (ATG) or other similar long-acting agents used for treatment of acute or chronic GvHD or administered during the conditioning regimen <90 days prior to randomization
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01380535

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Sponsors and Collaborators
Study Director: Christian Peters, MD Mallinckrodt
  More Information

Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT01380535     History of Changes
Other Study ID Numbers: 10-005  2010-022780-35 
Study First Received: June 22, 2011
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Italy: The Italian Medicines Agency
Germany: Paul-Ehrlich-Institut
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Austria: Agency for Health and Food Safety
Hungary: National Institute of Pharmacy

Keywords provided by Mallinckrodt:
Extracorporeal photopheresis therapy
Chronic graft versus host disease (cGvHD): National Institute Health Consensus Criteria

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Anti-Infective Agents
Antifungal Agents
Antirheumatic Agents
Calcineurin Inhibitors
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Photosensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016