A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 17
- 主要终点
- Determine the maximal tolerated dose (MTD)
研究概览
简要总结
A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response:
Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study.
Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression.
详细描述
Primary objectives
Phase I:
To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses
Phase II:
To confirm safety and hematological toxicity in 18 additional patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Myelodysplastic syndrome including the following WHO categories: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), WHO- AML with 20-30% marrow blasts (RAEB-T according to the FAB classification)
- •Prior treatment with Azacitidine or Decitabine for at least 6 courses without response (including CR, PR, marrow CR and stable disease with hematological improvement) or relapse after a response
- •IPSS score >1 (IPSS: Int-2 or High);
- •Age ≥ 18 years;
- •Normal liver function tests, defined by total bilirubin and transaminases less than 1.5 time the upper limit of normal;
- •Normal renal function, defined by creatinine less than 1.5 time the upper limit of normal, creatinine clearance ≥ 50 mL/min.
- •Patient ineligible for allogeneic hematopoietic stem cell transplantation;
- •Written informed consent;
- •Patient must understand and voluntarily sign consent form;
- •Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;
- •ECOG performance status between 0-2 at the time of screening;
- •Women of childbearing potential must:
- •Agree to use effective contraception without interruption throughout the study and for a further 1 month after the end of treatment;
- •Men must:
- •Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 1 month after the end of treatment if their partner is of childbearing potential.
排除标准
- •Severe infection or any other uncontrolled severe condition
- •Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months
- •Less than 30 days since prior treatment with growth factors (EPO, G-CSF)
- •Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
- •Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast;
- •Patient already enrolled in another therapeutic trial of an investigational drug;
- •HIV infection or active hepatitis B or C;
- •Women who are or could become pregnant or who are currently breastfeeding;
- •Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form;
- •Patient eligible for allotransplantation.
- •Known allergy to acadesine or any of its excipients
- •No affiliation to an insurance system
研究组 & 干预措施
ACADESINE 140mg/kg/d
3 patients will be included at the initial dose of Acadesine 140mg/kg/d
干预措施: ACADESINE 140mg/kg/d (Drug)
ACADESINE 210mg/kg/d
In absence of toxicity at the dose of 140mg/kg/d. There is a dose escalation of acadesine at the dose of 210mg/kg/d for 3 additionnal patients
干预措施: ACADESINE 210mg/kg/d (Drug)
ACADESINE 315mg/kg/d
In absence of toxicity at the dose of 210mg/kg/d. There is a dose escalation of acadesine at the dose of 315mg/kg/d for 3 additionnal patients
干预措施: ACADESINE 315mg/kg/d (Drug)
结局指标
主要结局
Determine the maximal tolerated dose (MTD)
时间窗: 6 month of treatment
Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression
次要结局
未报告次要终点