Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease

Phase 3

Terminated

Conditions: Steroid Refractory Acute Graft Versus Host Disease

Interventions: Drug: Methoxsalen
Procedure: Extracorporeal Photopheresis (ECP)

Registration Number: NCT02524847

Lead Sponsor: Therakos, Inc., a Mallinckrodt Company

Brief Summary: 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.

Detailed Description: Screening:

After the informed consent/assent form (ICF) is signed, the screening assessments will be performed in a single visit to establish the eligibility of the participant, based on inclusion and exclusion criteria, as well as aGvHD grading. Scheduling of the first week of ECP treatments and the arrangements for availability of typed and cross-matched donor packed red blood cells (PRBCs) for transfusion, if required, will be made in advance of participants entering the Treatment Period.

Treatment Period:

Once eligibility is established, participants will enter the 12-week ECP Treatment Period. The availability of typed and cross-matched donor PRBCs for transfusion during treatment, if needed, should be established prior to the scheduling of ECP treatments.

Participants will be allowed to continue standard aGvHD prophylaxis regimens (e.g., cyclosporine, tacrolimus, methotrexate, mycophenolate mofetil) without the addition of new therapies. Participants will be allowed to discontinue prophylaxis regimens for reasons of toxicity, and will also be allowed to switch to another prophylaxis medication within the same class (e.g., the calcineurin inhibitors cyclosporine and tacrolimus) for reasons of toxicity.

All participants enrolled in this trial will have received corticosteroids for the treatment of aGvHD. After entering the treatment period on study, tapering of steroids by total weekly decrements of 12.5% to 25% of the steroid dose at initiation of ECP therapy is permitted after a sustained response of aGvHD has been observed for at least 3 consecutive days, with the suggested goal to decrease the starting steroid dose by at least 50% 4 weeks after initiation of ECP.

Follow-Up Period:

After completion of the 12-week Treatment Period, participants may continue ECP treatment on commercial product at the Principal Investigator's discretion. Acute GvHD status will be assessed 4 weeks after completion of the Treatment Period. Participant survival will be assessed by passive follow-up (chart review) 26 weeks after initiation of ECP treatment.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Methoxsalen with ECP	Extracorporeal Photopheresis (ECP)	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Methoxsalen with ECP	Methoxsalen	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.

Primary Outcome Measures

Name	Time	Method
Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4	4 weeks	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

Secondary Outcome Measures

Name	Time	Method
Cumulative Dose of Daily Steroids	From diagnosis of aGvHD to 12 Weeks	Steroids administered from diagnosis of aGvHD to 12 Weeks after initiation of ECP treatment
Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8	8 weeks	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
Number of Participants With Adverse Events	16 weeks	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.
Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index	16 weeks	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.
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria	at 4, 8 and 12 weeks	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
Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12	12 weeks	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
Overall Response Rate (ORR) According to the Modified Glucksberg Criteria	4 weeks, 8 weeks, and 12 weeks	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.
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria	at 4, 8 and 12 weeks	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

Trial Locations

Locations (32): Phoenix Children's Hospital
🇺🇸
Phoenix, Arizona, United States
Children's Hospital of Los Angeles
🇺🇸
Los Angeles, California, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Children's Healthcare of Atlanta, Emory - Children's Center
🇺🇸
Atlanta, Georgia, United States
Lurie Children's Hospital
🇺🇸
Chicago, Illinois, United States
Boston Children's Hospital
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Boston, Massachusetts, United States
St. Louis Children's Hospital
🇺🇸
Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
University Hospitals Rainbow Babies & Children's
🇺🇸
Cleveland, Ohio, United States
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Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States