Extracorporeal Photopheresis Using Theraflex ECP™ for Patients With Refractory Chronic Graft Versus Host Disease (cGVHD)

NCT03083574 | Unknown Phase 2

• 1 other identifier: BHS-TC-11
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief Summary

The present project is a prospective, multicenter, non-randomized, phase II trial which aims to evaluate the clinical impact and the safety of extracorporeal photopheresis (ECP) using the Theraflex system in patients with refractory chronic graft versus host disease (cGVHD) after any type of hematopoietic stem cell transplantation or after donor lymphocyte infusion.

Conditions

Refractory Chronic Graft Versus Host Disease (cGVHD)

Keywords

Hematology; Chronic graft versus host disease (cGVHD); Extracorporeal photopheresis; Hematopoietic stem cell transplantation; Donor lymphocyte infusion

Outcome Measures

Primary Outcomes (5)

• Response rates of chronic GVHD to the Theraflex ECP treatment.

  Percentage of patients reaching complete response, percentage of patients reaching partial response.

  During the study (8 years and 2months)

• Duration of response.

  Time from achieving at least a partial response to the time of progression.

  During the study (8 years and 2months)

• GVHD-partial response survival.

  Time from partial response to either the first progression of GVHD or the date of death, whichever occurs first.

  During the study (8 years and 2months)

• GVHD-free Interval.

  Interval from the date of complete response to the date of the first progression of GVHD.

  During the study (8 years and 2months)

• GVHD-free survival.

  Time fromcomplete response to either the first progression of GVHD or the date of death, whichever occurs first.

  During the study (8 years and 2months)

Secondary Outcomes (4)

• Percentage of steroid dose saving.

  During the study (8 years and 2months)

• Discontinuation of immunosuppressive drugs during the ECP treatment

  During the study (8 years and 2months)

• Occurrence of adverse events and serious adverse events related to extracorporeal photopheresis.

  During the study (1 year of follow up after the last treatment)

• Incidence of viral, bacterial, fungal and parasitic infections

  During the study (8 years and 2months)

Study Arms (1)

Photopheresis Theraflex ECP™

EXPERIMENTAL

All patients will initially be treated by 6 cycles of extracorporeal photopheresis (i.e. extracorporeal photopheresis on two consecutive days) administered every 2 weeks. Patients will then be evaluated after 3 months and treatment continuation will be decided based on response.

Device: Photopheresis Theraflex ECP™

Interventions

Photopheresis Theraflex ECP™ DEVICE

The Macopharma (Theraflex ECP™) approach is based on a multistep procedure involving (1) standard mononuclear cell apheresis, (2) injection of the 8-Mop in the apheresis bag, (3) UVA exposure of the bag in the Macogenic illumination device, and (4) reinfusion of the cells into the patients.

Photopheresis Theraflex ECP™

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have chronic GVHD (cGVHD) occurring after any type of HSC transplantation : with any type of donor (HLA-identical siblings or HLA-matched or mismatched family or unrelated donor); with any type of conditioning (full-intensity, reduced-intensity, nonmyeloablative, no conditioning); with any type of HSC (bone marrow, PBSC, cord blood) or after donor lymphocyte infusion.
• Patients must have cGVHD that has already been treated with first-line systemic therapy for at least 1 month at effective doses. First-line systemic therapy must have included at least prednisolone 1 mg/kg/day or equivalent. In case of formal contraindication to steroid therapy, first-line systemic therapy must have included therapeutic doses of at least one of the following drugs: tacrolimus or ciclosporine (if patient not treated with a calcineurin inhibitor at onset of cGVHD), sirolimus, everolimus, mycophenolate mofetyl.
• Patients must require further salvage therapy for cGVHD because of either refractoriness or contraindication/intolerance to current therapy.
• Need for salvage therapy is defined by any of the following criteria :
• the development of 1 or more new sites of disease while being treated for chronic GVHD
• progression of existing sites of disease while receiving treatment for chronic GVHD
• failure to improve despite at least 1 month of standard treatment for chronic GVHD,
• relapse/progression of cGVHD while tapering current treatment for cGVHD.
• Patients may have received any number of previous lines of treatment for cGVHD.
• Concomitant treatment with other immunosuppressors is allowed if they were started and maintained at constant dosage for at least one month before the start of ECP. Shorter delay can be accepted for patients with highly progressive GVHD requiring salvage therapy.
• Signed informed consent.
• Any age.
• Weight \> 15 Kg (because of leukapheresis). Weight \<15 Kg is acceptable if a suitable method of leukapheresis has been developed and approved at site.

You may not qualify if:

• Patient has received any investigational agent for chronic GVHD in the past 4 weeks.
• Patient has started a new line of systemic therapy for cGVHD in the past 4 weeks. Shorter delay can be accepted for patients with highly progressive GVHD requiring salvage therapy.
• Known sensitivity to psoralen compounds such as 8-methoxypsoralen
• Comorbidities that may result in photosensitivity (coexisting skin cancer or photosensitive disease (such as porphyria, lupus, albinism…)
• Aphakia. MOP is contraindicated in patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses
• Known allergy to one of the components used in apheresis (e.g., heparin and citrate).
• History of heparin-induced thrombocytopenia or patients with serious coagulation disorders.
• Unable to tolerate the apheresis procedure including extracorporeal volume shifts because of uncompensated congestive heart failure, pulmonary edema, severe lung disease, severe renal failure, hepatic encephalopathy, or any other reason.
• Bilirubin \> 25 mg/L.
• Absolute neutrophil count \< 1.0 x 109 / L despite use of growth factors
• Platelet count \< 20 x 109 / L despite platelet transfusion
• HIV seropositivity.
• Uncontrolled infection
• Relapse or progression of the hematological malignancy.
• Eastern Cooperative Oncology Group (ECOG) score \> 2.

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Macopharma: collaborator
• Belgian Hematological Society: collaborator

Study Sites (8)

CHU Liège

Liège, Liège, 4000, Belgium

RECRUITING

Ziekenhuis Netwerk Antwerpen

Antwerp, 2060, Belgium

RECRUITING

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

RECRUITING

Institut Jules Bordet

Brussels, 1000, Belgium

RECRUITING

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 8000, Belgium

NOT YET RECRUITING

Universitair Ziekenhuis Brussel

Jette, 1090, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, 1200, Belgium

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Philippe Lewalle, MD, PhD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe Lewalle, MD, PhD

CONTACT

32-2-5417208; philippe.lewalle@bordet.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: March 20, 2017
• Study Start: September 1, 2014
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: March 20, 2017

Record last verified: 2017-03

Locations

BE (8)