Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host (Graft Versus Host, GVH) Did Not Respond to Imatinib Mesylate.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 22
- 主要终点
- Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)
研究概览
简要总结
Open label non-randomized multicenter phase 2 trial with direct individual benefice
详细描述
Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year. Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease), those who experience progression at any time, those who relapse after an initial response at any time or those who discontinue for toxicity at any time, will go to the salvage phase.
Salvage phase:
Nilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Induction phase (IM):
- •Patients aged ≥18 years to 75 years
- •Patients who underwent allo-SCT for a hematological disorder
- •Body weight ≥ 40 Kg.
- •Confirmed diagnosis of cGVHD resistant to at least one systemic immunosuppressive therapy. The diagnosis of cGHVD should be based on the NIH Working Group Consensus (www.asbmt.org/gvhd/index.htm). Grading of cGVHD will be based on clinical manifestations including:
- •ocular, oral and mucosal symptoms;
- •performance status;
- •evaluation of pulmonary functions;
- •cutaneous evaluation;
- •evaluation of musculo-skeletal manifestations;
- •evaluation of liver involvement;
- •Any source of hematopoietic stem cell is allowed
- •Both myeloablative and nonmyeloablative conditioning regimens are authorized.
- •Absence of contra-indications to the use of IM or Nilotinib
- •Patient having French health care coverage
- •Female patients of childbearing potential must have before initiation of study drug and agree to have efficient contraceptive precautions throughout the trial and for 3 months after the end of the trial.
- •Signed informed consent.
- •Salvage phase (Nilotinib) :
- •Patients enrolled in the first phase and who failed to IM:
- •Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease),
- •those who experience progression at any time,
- •those who relapse after an initial response at any time
- •or those who discontinue for toxicity at any time.
排除标准
- •Patient developing acute GVHD (whether early or "late onset" form)
- •First episode of cGVHD
- •Patient who received IM or Nilotinib treatment or any other TKI after transplant 3 months before the inclusion on the study
- •Patient treated by TKI for a GVHD
- •Contra-indication to IM or Nilotinib
- •Neutropenia < 0.5 G/L
- •Uncontrolled systemic infection which can be associated, according to the investigator, to an enhanced risk of patient's death during the first month of treatment
- •Severe neurological or psychiatric disorders
- •Pregnancy or lactation
- •Known uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction < 40% (cardiac tests as clinically indicated)
- •Recurrence of cancer for which the transplant was done except for presence of minimal residual disease by PCR
- •Patients with secondary malignancy ≤ 2 years prior study-entry except:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Prostate cancer (Tumor, Node, Metastasis [TNM] stage T1a or T1b)
- •Patients in emergency situation
- •Patients kept in detention
- •Patients unable or unwilling to comply with the protocol requirements
研究组 & 干预措施
open-label
Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year.
Salvage phase:
Nilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.
干预措施: Imatinib Mesylate and Nilotinib (Drug)
结局指标
主要结局
Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)
时间窗: Between Baseline and minimum 12 weeks of treatment
Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)
次要结局
- Best response to IM within 12 months and the duration of this response(From 12 to 52 weeks of Imatinib Mesylate treatment)
- use of systemic secondary treatment due to intolerance to Nilotinib(From baseline to 12 weeks of Nilotinib treatment)
- Best response rate to Nilotinib within 12 months and the duration of this response(From 12 to 52 weeks of Nilotinib treatment)
- use of systemic secondary treatment due to intolerance to IM(From baseline to 12 weeks of IM treatment)