Steroid Refractory Acute Graft Versus Host Disease Clinical Trial
Official title:
Single-Arm Study to Assess the Efficacy of UVADEX® (Methoxsalen) Sterile Solution in Conjunction With the THERAKOS® CELLEX® Photopheresis System in Pediatric Patients With Steroid-Refractory Acute Graft-vs-Host Disease (aGvHD)
| Verified date | July 2020 |
| Source | Mallinckrodt |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a single-arm, open-label, multicenter study of the efficacy of UVADEX® (methoxsalen) Sterile Solution in conjunction with THERAKOS® CELLEX® Photopheresis Systems (ECP) in pediatric participants with steroid-refractory aGvHD. The study is composed of Screening, Treatment, and Follow-up Periods.
| Status | Terminated |
| Enrollment | 29 |
| Est. completion date | July 16, 2019 |
| Est. primary completion date | July 16, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 21 Years |
| Eligibility |
Inclusion: 1. Male or female 1 to 21 years of age at the time of consent 2. Steroid-refractory grade B-D aGvHD. - Steroid-refractory is defined as a failure to respond to steroid treatment, with failure to respond defined as any grade B-D (IBMTR grading) aGvHD that shows progression = 3 days, or no improvement by 5 days of treatment with 2 mg/kg/day methylprednisolone or equivalent in participants with lower gastrointestinal (GI) or liver disease, or skin disease associated with bullae. Grade D organ involvement will be limited to skin and liver. - Steroid refractory may also be defined as a failure to respond to 1 mg/kg/day of methylprednisolone or equivalent in participants with disease confined to upper GI disease or lesser degrees of skin GvHD - Participants with lack of complete response after 2 weeks of steroid treatment 3. A Lansky scale Performance Status score = 30 4. Laboratory values are within the following limits, assessed within 3 days of the first study treatment: - Absolute neutrophil count > 0.5 × 10^9/liter (L) - Creatinine level < 2 times the upper limit of normal 5. For participants with isolated upper GI symptoms, pre-Screening biopsy results to confirm diagnosis of aGvHD 6. Female participants of childbearing potential and nonsterilized males who are sexually active with a female partner must be practicing highly effective, reliable, and medically approved contraceptive regimen throughout their participation in the study and for 3 months following the last ECP treatment. Or, for the US only, abstinence may be used in place of an approved contraceptive regimen. Females of childbearing potential are those who have reached the onset of menarche, or 8 years of age, whichever comes first. Approved contraceptive methods for female participants of childbearing potential or nonsterilized males who are sexually active with a female partner are as follows: - Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository - Established use of oral, injectable, or implanted hormonal methods of contraception. - Placement of an intrauterine device or intrauterine system 7. Signed informed consent/assent is obtained before conducting any study procedures; the parent, legal guardian, or legally authorized representative of a minor must also provide written informed consent Exclusion: 1. Currently enrolled in another clinical trial for the treatment of aGvHD 2. Use of any experimental regimens or medication(s) for aGvHD treatment 3. Treatment with > 2.0 mg/kg/day of methylprednisolone equivalents for aGvHD within 30 days prior to the first study treatment 4. Overt signs of relapse of the underlying condition 5. Uncontrolled viral, fungal, or bacterial infection 6. Platelet count < 20.0 × 10^9/L, despite platelet transfusion 7. Inability to tolerate the extracorporeal volume shifts associated with ECP treatment 8. Uncontrolled GI bleeding 9. Veno-occlusive liver disease 10. Life expectancy < 4 weeks 11. Participant requires invasive ventilation or vasopressor support 12. Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of seronegativity within 6 months of screening is required) 13. Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients 14. Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose Formula-A (ACD-A) 15. Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism) or aphakia 16. Coagulation disorders that cannot be corrected with simple transfusion 17. Co-existing melanoma, basal cell, or squamous cell skin carcinoma 18. Previous splenectomy 19. White blood cell count greater than 25,000 cubic millimeter (mm^3) 20. Currently being treated with any systemic immunosuppressive or biologic therapy for the treatment of a medical condition other than aGvHD 21. Female participant is breastfeeding or pregnant 22. Any medical concerns that may pose risk to the participant 23. Any psychological, familial, sociological, and/or geographical condition that may potentially hamper compliance with the study protocol and follow-up schedule |
| Country | Name | City | State |
|---|---|---|---|
| Austria | St Anna Kinderspital | Wien | |
| France | Hopital Necker Enfants Malades | Paris | |
| France | Hôpital universitaire Robert Debré | Paris | |
| Germany | Universitätsklinikum Leipzig, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Hämatologie und Internistische Onkologie | Leipzig | |
| Germany | Klinikum rechts der Isar, TU München, Klinik- und Poliklinik für Kinder- und Jugendmedizin, Kinderklinik München Schwabing | München | |
| Germany | University Hospital Tuebingen | Tübingen | |
| Germany | Universitaetsklinikum Ulm, Kinder- und Jugendmedizin | Ulm | |
| Hungary | United St Istvan and St Laszlo Hospital | Budapest | |
| Italy | U.O.C. Clinica di Oncoematologia Pediatrica Azienda Ospedaliera di Padova | Padova | |
| Italy | Pediatric Hospital Bambinu Gesu Rome | Rome | |
| Spain | Vall d'Hebron University Hospital | Barcelona | |
| Spain | Hospital Infantil Universitario "Nino Jesus" | Madrid | |
| Spain | University Hospital Salamanca | Salamanca | |
| Spain | Hospital LA FE | Valencia | |
| United Kingdom | Great North Children's Hospital (RVI) | Newcastle | |
| United States | Children's Healthcare of Atlanta, Emory - Children's Center | Atlanta | Georgia |
| United States | Boston Children's Hospital | Boston | Massachusetts |
| United States | Lurie Children's Hospital | Chicago | Illinois |
| United States | Cleveland Clinic Children's | Cleveland | Ohio |
| United States | University Hospitals Rainbow Babies & Children's | Cleveland | Ohio |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | MD Anderson Cancer Care Center | Houston | Texas |
| United States | Children's Hospital of Los Angeles | Los Angeles | California |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Vanderbilt University Medical Center - Ingram Cancer Institute | Nashville | Tennessee |
| United States | Yale University | New Haven | Connecticut |
| United States | Phoenix Children's Hospital | Phoenix | Arizona |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | St. Louis Children's Hospital | Saint Louis | Missouri |
| United States | University of Utah | Salt Lake City | Utah |
| United States | Fred Hutchinson Cancer Research Center | Seattle | Washington |
| United States | Children's National Medical Center | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Therakos, Inc., a Mallinckrodt Company |
United States, Austria, France, Germany, Hungary, Italy, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4 | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment |
4 weeks | |
| Secondary | Number of Participants With Adverse Events | Clinically significant changes in vital signs, laboratory values and investigations are reported as adverse events. Summary data are provided below, with details listed in the adverse events module. | 16 weeks | |
| Secondary | Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8 | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment |
8 weeks | |
| Secondary | Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12 | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment |
12 weeks | |
| Secondary | Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index | Duration of first response is presented for patients whose disease progressed. Duration of response is defined in the following way: Patients whose response failed: Date at which 1st disease progression occurs - date of 1st response +1. Patients whose response did not relapse: Date of 16 week follow-up or final assessment prior to week 16 (if patient withdrew early) - date of 1st response. |
16 weeks | |
| Secondary | Overall Response Rate (ORR) According to the Modified Glucksberg Criteria | ORR is defined as the percentage of patients who achieve an overall response after 4 weeks, 8 weeks, and 12 weeks of ECP treatment according to a scoring algorithm applied to calculate the grade of aGvHD using the modified Glucksberg Criteria. | 4 weeks, 8 weeks, and 12 weeks | |
| Secondary | Cumulative Dose of Daily Steroids | Steroids administered from diagnosis of aGvHD to 12 Weeks after initiation of ECP treatment | From diagnosis of aGvHD to 12 Weeks | |
| Secondary | Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria | Number of patients whose skin was rated as Stage 0 - 4 using the modified Glucksberg criteria based on the Graft versus Host Disease (GvHD) rash - Stages are defined as 0=No GvHD rash, 1=Maculopapular rash on <25% body surface area (BSA), 2=Maculopapular rash on 25-50% BSA, 3=Maculopapular rash on >50% BSA, and 4=Generalized erythroderma plus bullous formation, which are blisters bigger than 5 mm across | at 4, 8 and 12 weeks | |
| Secondary | Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria | Number of patients whose liver was rated as Stage 0 - 4 on the modified Glucksberg criteria - Stages are based on level of bilirubin, defined as: Stage 0 = Bilirubin < 2.0 mg/dL, Stage 1 = Bilirubin 2.0-3.0 mg/dL, Stage 2 = Bilirubin 3.1-6.0 mg/dL, Stage 3 = Bilirubin 6.1-15.0 mg/dL, and Stage 4 = Bilirubin > 15.0 mg/dL | at 4, 8 and 12 weeks |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| No longer available |
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Early Access Program Using Alpha 1 Antitrypsin Infusion for Patients With Steroid Refractory Acute GvHD After Hematopoietic Stem Cell Transplantation (HSCT)
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