Chronic graft-versus-host disease (cGvHD) MedDRA version: 14.1 Level: PT Classification code 10018651 Term: Graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: UVADEX™
Product Name: methoxsalen
Pharmaceutical Form: Solution for blood fraction modification
INN or Proposed INN: methoxsalen
Sponsors
THERAKOS, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are able to provide written informed consent. 2. Patients with new onset moderate or severe cGvHD per NIH Consensus Criteria (for staging and severity) definition as assessed by the NIH Consensus Criteria Clinical Assessment (NIH Clinical Assessment Forms and instructions are provided in Study Reference Manual) with onset within 3 years of transplantation. 3. Willingness to start treatment with 1.0 mg/kg prednisone, or equivalent, at baseline. 4. Patients with prior acute GvHD symptoms 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 acute GvHD is permitted in the study. 5. Age = 18 years. 6. Weight > 40 kg. 7. Platelet count > 25,000/µL (including platelet support). 8. Eastern Cooperative Oncology Group (ECOG) score of 0-2. 9. Life expectancy of at least 3 months with no imminent relapse expected. 10. Women of childbearing potential and all men must be using adequate birth control measures (e.g., abstinence, oral contraceptive, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the study. 11. Women with childbearing potential must provide a negative pregnancy test within 10 days before study start. 12. Patients must be able and willing to comply with all study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Corticosteroid intolerance, based on previous clinical experience. 2a. Previous treatment with >2.0 mg/kg daily prednisone, or equivalent, during the 7 days prior to the baseline visit. 2b. Previous treatment with systemic steroids for moderate to severe chronic GvHD for more than 7 days prior to the baseline visit. 2c. Previous treatment for mild cGvHD with >0.5 mg/kg of prednisone or equivalent during the 2 weeks prior to screening. 3. Evidence of known infection with human immunodeficiency virus (HIV) or active (not including latent) Hepatitis B (laboratory testing is not required if virus status is already known). 4. Requires treatment with budesonide and similar low absorption oral steroids and steroid enema preparations. Patients who have discontinued these medications at screening will be eligible for the study. 5. Expected to receive donor lymphocyte infusion (DLI). Patients who have received DLI in the past are still eligible for the study. 6. Uncontrolled infection requiring treatment at study entry. 7. Known definite bronchiolitis obliterans (biopsy proven). 8a. Patients who are receiving myciphenolate mofetil (MMF), tyrosine kinase inhibitors (TKIs), such as imatinib, sunitinib and dasatinib), anti-tumor necrosis factor (TNF agents, sirolimus and bortezomib or patients who are receiving PUVA therapy. Patients who have discontinued these medications or PUVA at screening will be eligible for the study. If MMF needs to be tapered, the taper should start at screening and be completed (i.e., medication discontinued) by Day 7 post baseline. 8b. Patients who are receiving alemtuzumab, antithymocyte globulin (ATG) or other similar pharmacologically long-acting agents used for treatment of acute or chronic GvHD or administered during the conditioning regimen <90 days prior to randomization. 9. Hypersensitivity or allergy to psoralen (methoxsalen). 10. Hypersensitivity or allergy to both heparin and citrate products. (If hypersensitive or allergic to only one of these two products, exclusion does not apply). 11. Inability to tolerate fluid changes associated with ECP (e.g., inadequate renal, hepatic, pulmonary and cardiac function leading to enable patient to tolerate extracorporeal volume shifts associated with ECP). 12. Presence of aphakia or photosensitive disease (systemic lupus erythromatosus, porphyrias, albinism, etc.). If the eye with aphakia has no vision capabilities then the patient may be included in the study. 13. Women who are pregnant and/or lactating. 14. Have used any investigational drug/treatment within the previous 28 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint will be the Week 28 overall response (complete response [CR] or partial response [PR]) according to NIH Consensus Response Criteria. Safety endpoints for each patient will include relapse of underlying malignancy, vital signs, laboratory testing, including chemistry panel and complete blood count, and adverse event (AE) reporting, including AEs from active standard of care medication. Relapses of underlying malignancy will not be considered as AE. This will be captured and analysed separately from AEs. Patients who have relapsed of underlying malignancy will be discontinued from the study. Also, any AEs resulting from study treatment occuring or continuing outside of the 28-week period will be reported. ;Main Objective: To compare the efficacy of ECP (Extracorporeal photopheresis) as determined by the incremental improvement in cGvHD (chronic graft-versus-host disease) according to National Institutes of Healt (NIH) Consensus Response Criteria versus a control population.; Secondary Objective: To assess changes in individual organ systems involved in cGvHD as assessed by NIH Consensus Response Criteria through Week 28. To perform sensitivity analyses on the NIH Consensus (response and severity) Criteria and correlate with the investigators' assessments through Week 28. To correlate changes in the total skin score (TSS) instrument to the NIH Consensus Criteria Clinical Assessment in all patients with cutaneous disease through Week 28. To assess the efficacy of THERAKOS photopheresis systems (UVAR XTS and CELLEX) through Week 28. To assess the QoL for both treatment arms through Week 28. To assess the cumulative corticosteroids dose through Week 28. To evaluate the safety of the treatment arms through Week 28. To capture an | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportions of patients in each treatment group achieving response rates (CR or PR) by organ involvement through use of the NIH Consensus Response Criteria through Week 28. Correlation between TSS and skin assessment using NIH Consensus Criteria CLinical Assessment through Week 28. Sensitivity analyses on the NIH Consensus [(response and severity) (for example, considering alternative diagnoses and using one stage improvement response criteria)] Criteria and correlation with the investigators' assessments through Week 28. QoL assessment through Week 28. Efficacy data for THERAKOS UVAR XTS and CELLEX Photopheresis Systems through Week 28. Efficacy assessment by baseline risk (high risk defined as patients with platelet count <100,000/µL at baseline) and severity of cGvHD. Cumulative dose of corticosteroids through Week 28. Additional endpoints are associated with the long term follow-up. ;Timepoint(s) of evaluation of this end point: Week 28 for all except the last one. The biomarker collect for all patients will end at week 28, but the testing will take afterwards. | — |
Countries
Austria, France, Germany, Hungary, Italy, Spain, United Kingdom, United States
Contacts
Public ContactSafety Center
PAREXEL International Safety Center
Outcome results
None listed