Clinical trial NCT03083574: Extracorporeal Photopheresis Using Theraflex ECP™ for Patients With Refractory Chronic Graft Versus Host Disease (cGVHD)
Official title: A Phase II Study to Assess the Safety and the Efficacy of Extracorporeal Photopheresis Using the Theraflex ECP™ for Patients With Refractory Chronic Graft Versus Host Disease (cGVHD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
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
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: Macopharma
name: Belgian Hematological Society
First posted: 2017-03-20
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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 primarily affecting at least one of the following organs: skin; oral mucosal; eye; liver; lung; joints; fascia. Gastro-intetinal (GI) cGVHD alone is not a sufficient inclusion criterion.
* 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.

Exclusion Criteria:

* 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.
* Pregnancy or breastfeeding
* Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment.
* Any serious illness with expected survival less than 6 months.
* Any clinically significant medical or other condition that in the investigator's opinion could interfere with the administration of photopheresis or interpretation of study results, or compromise the safety or wellbeing of the patient.

Primary outcomes:
measure: Response rates of chronic GVHD to the Theraflex ECP treatment.
timeFrame: During the study (8 years and 2months)
measure: Duration of response.
timeFrame: During the study (8 years and 2months)
measure: GVHD-partial response survival.
timeFrame: During the study (8 years and 2months)
measure: GVHD-free Interval.
timeFrame: During the study (8 years and 2months)
measure: GVHD-free survival.
timeFrame: During the study (8 years and 2months)
Secondary outcomes:
measure: Percentage of steroid dose saving.
timeFrame: During the study (8 years and 2months)
measure: Discontinuation of immunosuppressive drugs during the ECP treatment
timeFrame: During the study (8 years and 2months)
measure: Occurrence of adverse events and serious adverse events related to extracorporeal photopheresis.
timeFrame: During the study (1 year of follow up after the last treatment)
measure: Incidence of viral, bacterial, fungal and parasitic infections
timeFrame: During the study (8 years and 2months)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Liège
country: Belgium
facility: CHU Liège
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
Study officials:
affiliation: Jules Bordet Institute
name: Philippe Lewalle, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: