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

NCT02524847 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: TKS-2014-001
• Study Type: interventional
• Target: 29
• Locations: 8 countries
• Sites: 32

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.

Conditions

Steroid Refractory Acute Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants With Adverse Events

  16 weeks

• Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8

  8 weeks

• Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12

  12 weeks

• Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index

  16 weeks

• Overall Response Rate (ORR) According to the Modified Glucksberg Criteria

  4 weeks, 8 weeks, and 12 weeks

Study Arms (1)

Methoxsalen with ECP

EXPERIMENTAL

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.

Drug: Methoxsalen; Procedure: Extracorporeal Photopheresis (ECP)

Interventions

Methoxsalen DRUG

Sterile solution used in conjunction with photopheresis procedure.

Also known as: UVADEX®

Methoxsalen with ECP

Extracorporeal Photopheresis (ECP) PROCEDURE

Also known as: THERAKOS® CELLEX® Photopheresis System

Methoxsalen with ECP

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female 1 to 21 years of age at the time of consent
• 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
• A Lansky scale Performance Status score ≥ 30
• 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
• For participants with isolated upper GI symptoms, pre-Screening biopsy results to confirm diagnosis of aGvHD
• 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
• 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

You may not qualify if:

• Currently enrolled in another clinical trial for the treatment of aGvHD
• Use of any experimental regimens or medication(s) for aGvHD treatment
• Treatment with \> 2.0 mg/kg/day of methylprednisolone equivalents for aGvHD within 30 days prior to the first study treatment
• Overt signs of relapse of the underlying condition
• Uncontrolled viral, fungal, or bacterial infection
• Platelet count \< 20.0 × 10\^9/L, despite platelet transfusion
• Inability to tolerate the extracorporeal volume shifts associated with ECP treatment
• Uncontrolled GI bleeding
• Veno-occlusive liver disease
• Life expectancy \< 4 weeks
• Participant requires invasive ventilation or vasopressor support
• Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of seronegativity within 6 months of screening is required)
• Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients
• Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose Formula-A (ACD-A)
• Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism) or aphakia

Sponsors & Collaborators

• Therakos, Inc., a Mallinckrodt Company: lead

Study Sites (32)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta, Emory - Children's Center

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University Hospitals Rainbow Babies & Children's

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Children's

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University Medical Center - Ingram Cancer Institute

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Care Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

St Anna Kinderspital

Vienna, 1090, Austria

Location

Hopital Necker Enfants Malades

Paris, 75015, France

Location

Hôpital universitaire Robert Debré

Paris, 75019, France

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Hämatologie und Internistische Onkologie

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar, TU München, Klinik- und Poliklinik für Kinder- und Jugendmedizin, Kinderklinik München Schwabing

München, 80804, Germany

Location

University Hospital Tuebingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Ulm, Kinder- und Jugendmedizin

Ulm, 89075, Germany

Location

United St Istvan and St Laszlo Hospital

Budapest, 1097, Hungary

Location

U.O.C. Clinica di Oncoematologia Pediatrica Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Pediatric Hospital Bambinu Gesu Rome

Rome, 00165, Italy

Location

Vall d'Hebron University Hospital

Barcelona, 8035, Spain

Location

Hospital Infantil Universitario "Nino Jesus"

Madrid, 28009, Spain

Location

University Hospital Salamanca

Salamanca, 37007, Spain

Location

Hospital LA FE

Valencia, 46026, Spain

Location

Great North Children's Hospital (RVI)

Newcastle, NE1 4LP, United Kingdom

Location

MeSH Terms

Interventions

Methoxsalen; Photopheresis

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Limitations and Caveats

This study did have a notable limitation in its single-group study design. This may limit a more robust assessment vs standard of care alone for primary endpoint of overall response and secondary endpoints steroid sparing and disease progression.

Results Point of Contact

• Title: Medical Information Call Center
• Organization: Mallinckrodt Pharmaceuticals

clinicaltrials@mnk.com

800-844-2830

Study Officials

• Clinical Team Leader

  Mallinckrodt

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: August 17, 2015
• Study Start: January 20, 2016
• Primary Completion: July 16, 2019
• Study Completion: July 16, 2019
• Last Updated: September 11, 2020
• Results First Posted: September 11, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); HU (1); US (17); DE (4); GB (1); FR (2); ES (4); IT (2)