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)
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Response rates of chronic GVHD to the Theraflex ECP treatment.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Weight > 15 Kg (because of leukapheresis). Weight <15 Kg is acceptable if a suitable method of leukapheresis has been developed and approved at site.
排除标准
- •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 >
- •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.
研究组 & 干预措施
Photopheresis Theraflex ECP™
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.
干预措施: Photopheresis Theraflex ECP™ (Device)
结局指标
主要结局
Response rates of chronic GVHD to the Theraflex ECP treatment.
时间窗: During the study (8 years and 2months)
Percentage of patients reaching complete response, percentage of patients reaching partial response.
Duration of response.
时间窗: During the study (8 years and 2months)
Time from achieving at least a partial response to the time of progression.
GVHD-partial response survival.
时间窗: During the study (8 years and 2months)
Time from partial response to either the first progression of GVHD or the date of death, whichever occurs first.
GVHD-free Interval.
时间窗: During the study (8 years and 2months)
Interval from the date of complete response to the date of the first progression of GVHD.
GVHD-free survival.
时间窗: During the study (8 years and 2months)
Time fromcomplete response to either the first progression of GVHD or the date of death, whichever occurs first.
次要结局
- 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))