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

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Mallinckrodt
ClinicalTrials.gov Identifier:
NCT01380535
First received: June 22, 2011
Last updated: May 17, 2017
Last verified: May 2017
  Purpose
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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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 ]
    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


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 ]
    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


Enrollment: 60
Actual Study Start Date: November 2011
Study Completion Date: March 10, 2017
Primary Completion Date: March 10, 2017 (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.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Long term follow up: Enrolled into the primary study and provide written 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380535

  Show 32 Study Locations
Sponsors and Collaborators
Mallinckrodt
Parexel
  More Information

Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT01380535     History of Changes
Other Study ID Numbers: 10-005
2010-022780-35 ( EudraCT Number )
Study First Received: June 22, 2011
Last Updated: May 17, 2017

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

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Prednisone
Cyclosporins
Cyclosporine
Tacrolimus
Methoxsalen
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Photosensitizing Agents

ClinicalTrials.gov processed this record on June 21, 2017