A Dose-finding Phase I/II Trial of Daunorubicin and Cytarabine Combined to Fractionated Mylotarg® as Re-induction Treatment in Patients With First Relapse of Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 9
- 主要终点
- Dose-limiting toxicity (DLT) defined by the occurrence of any G3 or G4 non reversible toxicity at day 45 excluding myelosuppression or infection due to neutropenia, and response defined by complete remission at day 45
研究概览
简要总结
For several years, the effective standard induction chemotherapy for AML has been limited to the association of anthracycline and aracytine. GO is the first effective targeted antibody used in leukemia patients. In a previous study, we showed efficacy and safety of fractionated doses of GO used as a single agent for treatment of adult AML patients in first relapse. In the present study the possibility of combining fractionated doses of GO to escalated doses of a 3+7 regimen old is studied in relapsed AML patients > 50 and <70 years.
详细描述
Induction course are:
GO 3mg/m2 on days 1, 4,7 + the three dose levels were as follows:
level 1: DNR: 45 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 2: DNR: 60 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 3: DNR 60 mg/m2 x 3 days + AraC: 200 mg/m2 x 7 days. with 20 mg of methylprednisolone prior to each GO infusion. Consolidation course: patients in CR may receive 2 additional courses of consolidation chemotherapy with Amsacrine 90 mg/m2 daily for 3 days, and Ara-C (1g/m2/12 hours x 3 days) + GO 3 mg/m2 on day 1.
Treatment with HSCT is offered at the discretion of the physician in charge of the patient. A delay between last infusion of GO and HSCT above 3 months is recommended
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a morphologically proven diagnosis of CD33-positive AML and :
- •Age ≥ 50 years and ≤ 70 years.
- •First relapsing AML with a duration of first CR ≥ 3 and ≤18 months
- •ECOG performance status 0 to 3
- •Negative serology HIV, HBV and HBC (except post vaccination)
- •Serum creatinine ≤ 2N; AST and ALT ≤ 2N; total bilirubin ≤ 2N
- •Cardiac function determined by radionuclide or echography within normal limits.
- •Negative serum pregnancy test within one week before treatment for women of child bearing potential
- •Signed informed consent.
排除标准
- •AML following diagnosed myelodysplastic syndrome or myeloproliferation
- •Known central nervous system involvement with AML
- •Prior treatment with HSCT.
- •Previous treatment with Anti CD33 antibodies
- •Uncontrolled infection
- •Other active malignancy
研究组 & 干预措施
DAUNORUBICINE - ARACYTINE - MYLOTARG -
Adaptive Bayesian method for dose-finding in phase I/II clinical trials based on treatment efficacy and toxicity (Thall, Russel, 1998), with successive patients cohorts and three combined dose levels:
DNR 45 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7.
DNR 60 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7.
DNR 60 mg/m2 IV days 1 to 3 + AraC 200 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7.
Two consolidation courses for CR patients:
Amsacrine: 90 mg/m2 IV Day 1 Cytarabine: 1g/m2 twice a day IV Days 1 to 4 Mylotarg: 3 mg/m2 IV Day 1.
干预措施: Mylotarg (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT) defined by the occurrence of any G3 or G4 non reversible toxicity at day 45 excluding myelosuppression or infection due to neutropenia, and response defined by complete remission at day 45
时间窗: Day 45 post first dose of treatment
次要结局
- Secondary endpoint: Duration of second remission in AML patients treated for relapse with chemotherapy + Mylotarg as re-induction and consolidation.(At two years)