Phase II Trial of Combined Immunochemotherapy With Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients With Previously Treated or Untreated T-Prolymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Remission Rate
研究概览
简要总结
Study hypothesis: Simultaneous FMC-Alemtuzumab administration followed by Alemtuzumab maintenance therapy in patients with T-PLL is feasible, safe and efficient.
详细描述
As the median survival time of patients with T-PLL is less than 12 months, the treatment of T-PLL is a special challenge.
The overall response rates with conventional chemotherapy or Deoxycoformycin were low (about 30% and 40%), with the monoclonal antibody Alemtuzumab response rates of 50% to 70% were achieved, but the duration of the response was short.
In the previous trial (T PLL 1), the efficacy of the FMC regimen (FMC = Fludarabine, Mitoxantrone and Cyclophosphamide) was tested, a preliminary analysis of 16 patients revealed a response rate of more than 60% after FMC-polychemotherapy and 83% after the subsequent administration of Alemtuzumab.
The goal of the T-PLL2-protocol is to assess if the simultaneous administration of FMC-polychemotherapy and Alemtuzumab with a subsequent Alemtuzumab maintenance therapy is capable of improving the remission rate and the disease-free survival time in patients with T-PLL.
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
- •Untreated patients with T-prolymphocytic leukemia (T-PLL) according to WHO criteria or pretreated patients (max. one previous treatment) with T-PLL
- •Age ≥ 18 years
- •WHO performance status of 0-2
- •Life expectancy > 6 months
- •CIRS score >= 6
- •Left ventricular ejection fraction ≥50% confirmed by echo-cardiogram performed < 6 months before inclusion to the trial and after the end of a possible anthracycline containing pretreatment
- •Adequate liver function as indicated by a total bilirubin, AST and ALT >= 2 the institutional ULN value, unless directly attributable to the T-PLL
- •Creatinine clearance >= 70 ml/min calculated according to the formula of Cockcroft and Gault
- •Seronegativity for HIV, HBV or HCV confirmed by serological testing within 6 weeks prior to registration
- •Willingness of fertile male and female patients to use a highly effective contraceptive method with a Pearl-Index < 1 during and at least six months after the end of the study treatment (e.g. implants, injectables, oral contraceptives in combination with another contraceptive method, some IUDs, sexual abstinence or vasectomised partner)
- •Negative serum pregnancy test one week prior to treatment (required for female patients before and <2 years after onset of menopause)
- •Patient's written informed consent
排除标准
- •Clinically significant auto-immune cytopenia or clinically significant hemolytic anaemia with suspicion of immune origin, even if Coombs test is negative
- •Active secondary malignancy requiring treatment (except basal cell carcinoma or tumour curatively treated by surgery)
- •Medical condition requiring prolonged use of oral corticosteroids (> 1 month)
- •Cerebral dysfunction, legal incapacity
- •Any circumstance at the time of study entry that would preclude completion of the study and required follow-up
- •Active infection or severe infection (WHO 4th degree) within the last three months before inclusion to the study
- •Participation in any other clinical trial during this study
- •Known hypersensitivity to any of the study medications (Fludarabine, Cyclophosphamide, Mitoxantrone or Alemtuzumab)
- •Patients who have already received more than 60% of the recommended maximum cumulative dose of an anthracycline (Epirubicine, Adriamycine or Mitoxantrone).
- •This maximum cumulative dose is defined for the individual substances as follows:
- •Epirubicin 900 mg/m²
- •Daunorubicin 550 mg/m², (or 400 mg/m² if the patient received mediastinal irradiation)
- •Adriamycine (Doxorubicine) 550 mg/m²
- •Mitoxantrone 200 mg/m²
- •Patients who already received Fludarabine in combination with Cyclophosphamide or Mitoxantrone
- •Patients who received prior treatment with Alemtuzumab alone or in combination with a purine analogue and who did not achieve a PR that lasted at least 6 months
- •Patients who are employees of the Sponsor (University of Cologne) or the study sites.
研究组 & 干预措施
FCM-A followed by A-maintenance
First treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c.
干预措施: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (Drug)
FCM-A followed by A-maintenance
First treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c.
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Remission Rate
时间窗: 2 years after trial started
Efficacy of the FMC therapy and Alemtuzumab Percentage and 95%-confidence-interval of response rates (CR, CRi, nPR, PR, SD and PD) will be provided.
次要结局
- Overall Survival Time(4 years after start of trial)