Phase II Multicenter Study of Extracorporal Photopheresis with UVADEX Plus Standard Steroid Treatment for High Risk Acute Graft-versus-host Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- The proportion of complete response CR (that is, per-cent of patients with skin, liver, and GI GvHD all stage 0) at day 28 of study treatment.
研究概览
简要总结
This is a single arm phase 2 trial which includes patients with high risk acute GVHD defined as Ann Arbor score 2 or 3. The purpose of the study is to improve the outcome of these patients in terms of response to treatment and treatment related mortality. All patients will receive the study intervention (ECP with Uvadex). The study hypothesis is that the treatment plan will produce a day 28 complete response rate higher than or equal to 52%, which will represent an improvement of 15% compared with the standard of care (37%). The rate of complete response to standard of care treatment is based on observed data in similar patients treated within the Mount Sanai Acute GVHD International Consorium (MAGIC). Patients will be treated for 56 days and followed for one year to also enable evaluation of long term outcome.
详细描述
This study is a single arm phase 2 study for adult patients who have acute GVHD Grade II-IV according to Glucksberg and Ann Arbor score 2 or 3 after first allogeneic stem cell transplantation. The staging according to Glucksberg is based on clinical parameters while Ann Arbor scoring is based on the MAGIC biomarkers. Patients will receive standard acute GVHD treatment consisting of 2mg/kg methylprednisolone plus extracorporeal photopheresis (ECP) with Uvadex. Day 0 of the study will be the first day of ECP, which will be performed 3x weekly for the first 2 weeks, 2x weekly for the next two weeks and thereafter once weekly until day 56. A taper schema for methylprednisolone is proposed but not obligatory. Patients will be followed until one year after start of ECP.
The study plans to enroll 72 patients in order to be able to detect a 15% difference in rate of complete responses on day 28, assuming a type I error rate of 0.05. Patients treated on this study will have three possible comparators:
- Cohort of patients with high risk aGvHD who received standard treatment and whose data were prospectively reported to MAGIC during the last 2 years preceding the trial
- Cohort of patients with high risk aGvHD who received standard treatment and whose data are reported to MAGIC during the trial period
- Cohort of patients with high risk aGvHD treated within the ongoing prospective MAGIC USA phase 2 Trial
Treatment:
Prior to an ECP treatment each patient will be assessed by a physician to verify that the patient is acceptable for ECP treatment. This assessment will include vital signs (diastolic and systolic blood pressures, pulse, temperature) which will be taken prior to and at the end of each ECP treatment. Blood cell counts will be analyzed prior to each treatment. If a patient's WBC count is below 1 X 109/L or platelet count is below 20 X 109/L ECP should be postponed until rise in WBC or platelet counts. Platelet transfusions and use of cytokines is permitted. Whenever possible, peripheral venous access is preferable to central venous catheters. In patients with platelet counts below 40 X 109/L acid citrate dextrose (ACD) instead of heparin should be used for ECP. When severe acute infections occur during study ECP should be discontinued until the infection has been controlled under appropriate therapy
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
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New onset high risk acute GvHD (Ann Arbor score 2/3 as defined in Appendix A) following allogeneic SCT. Any clinical severity in accordance with Glucksberg grade II-IV is eligible.
- •Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.
- •No prior systemic treatment for acute GvHD except for a maximum of 7 days of methylprednisolone ≤2 mg/kg/day (or IV methylprednisolone equivalent) during the period from initiation of systemic steroid treatment for acute GvHD until study therapy begins. Topical skin steroid treatment and non-absorbable oral steroid treatment for GI GvHD are permissible.
- •Age 18 years or older.
- •Platelet count > 25.000 (including platelet support)
- •Eastern Coorperative Oncology Group (ECOG) score of 0≤2 unless due to aGvHD
- •Negative pregnancy test within 10 days before start of study if the patient is a woman of child-bearing Age
- •Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGvHD within 3 days before screening.
- •ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days before screening.
- •Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.
- •Written informed consent from patient.
- •Biopsy of acute GvHD target organ is strongly recommended but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 5 working days of Initiation of systemic steroid treatment for acute GvHD are not permitted to participate
排除标准
- •Progressive or relapsed malignancy
- •Uncontrolled active infection
- •Patients with chronic GvHD
- •History of or current diagnosis of progressive multifocal leukoencephalopathy (PML)
- •Pregnant or nursing (lactating) women
- •Use of other drugs for the treatment of acute GvHD apart from ongoing GvHD prophylaxis and corticosteroids
- •Patients on dialysis
- •Patients requiring ventilator support
- •Evidence of known infection with human immunodeficiency virus (HIV) or active hepatitis B
- •Investigational agent within 30 days of enrollment without approval from the Sponsor/ Investigator (PI). (Off-label use of medication is not considered investigational unless in context of a formal study)
- •History of allergic reaction to 8-MOP
- •Concomitant diagnosis of malignant melanoma or basal cell carcinoma
- •Hypersensitivity or allergy to both heparin and citrate products (if hypersensitive or allergic only to one, exclusion does not apply)
- •Inability to tolerate extracorporeal volume shifts associated with ECP
- •Presence of aphakia
- •History of splenectomy
- •Leucocyte count > 25.000/μl
- •Coagulopathy
- •Known photosensitive disease like systemic lupus erythematosus, porphyrias or albinism
研究组 & 干预措施
Extracorporeal photopheresis (ECP) with Uvadex
Patients in this single Arm study all receive the intervention consisting of ECP with Uvadex plus the standard of care treatment which consists of systemic corticosteroids 2mg/kg. Response to treatment will be evaluated on day 28. Patients will receive study treatment till day 56 and thereafter be followed until 1 year.
干预措施: Uvadex (Drug)
结局指标
主要结局
The proportion of complete response CR (that is, per-cent of patients with skin, liver, and GI GvHD all stage 0) at day 28 of study treatment.
时间窗: day 28
次要结局
- Overall survival at 1 year(1 year)
- Cumulative incidence of NRM(6 months and at 1 year)
- Overall response rate (complete response + partial response)(day 28 and day 56)
- Cumulative incidence of treatment-refractory GvHD(day 28)
- Cumulative incidence of severe GI GvHD (Grade 3 and 4)(through study completion, an average of 1 year)
- Time to discontinuation of steroid therapy(Start to end of steroid treatment. Time to discontinuation of steroid treatment will be assessed from start of steroid treatment up to relapse of underlying disease, death from any cause or up to 12 months after start of treatment, whichever came first.)
- Number of lines of GvHD therapy(through study completion, an average of 1 year)
- Cumulative incidence of chronic GvHD(through study completion, an average of 1 year)
- Number of serious infections(through study completion, an average of 1 year)