SAFETY AND EFFICACY OF PENTOXIFYLLINE VERSUS PLACEBO ADMINISTERED AS APOPTOSIS INDUCTOR DURING REMISSION INDUCTION PHASE OF PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Apoptosis measure by Flow Cytometry
研究概览
简要总结
Recent advances in acute lymphoblastic leukemia treatment are based on a cytotoxic drug combination. Measurement of minimal residual disease in bone marrow samples at day 14 of treatment is the most powerful early predictive indicator of further relapse, and it can be applied practically to all patients with acute lymphoblastic leukemia. Even more so, it has been observed that patients who present negative minimal residual disease in bone marrow samples at day 7 during induction have a better prognosis than those achieving this at day 14.
Relapse represents the main cause of treatment failure that related in the extreme with resistance to apoptosis, defining the latter as the principal mechanism of programmed cell death; it is also related with the induction of leukemic cells to senescent arrest.
Pentoxifylline is a methyl-xanthine byproduct considered an unspecific inhibitor of phosphodiesterase. It inhibits nuclear factor-kappa-beta activation by different mechanisms and stimulates apoptosis induced by different drugs; thus, it can optimize the antineoplastic effect of actual treatments in order to increase the apoptosis of leukemic cells. This effect might improve the prognosis of these patients.
Evaluate the safety and effect of Pentoxifylline together with antineoplastic drugs in order to study increased apoptosis and decreased senescence during the remission induction phase in pediatric patients with newly diagnosed acute lymphoblastic leukemia. To achieve this propose, we will divide patients in two groups, who will receive pentoxifylline or placebo depending on the group, in addition to conventional treatment according to the protocol standard chemotherapy schema for pediatric patients with acute lymphoblastic leukemia at our institution during the remission induction phase. In addition, we will test whether the study group exerts an impact on reaching remission earlier as compared with the control group.
详细描述
This study will be controlled, double-blind clinical trial versus placebo, with random assignment to evaluate the effect of pentoxifylline on apoptosis and senescence of leukemic blasts from remission induction in pediatric patients with newly diagnosed acute lymphoblastic leukemia, as well as to address pentoxifylline efficacy and safety in this group of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric and teenaged patients of both genders ≤18 years of age with newly diagnosed acute lymphoblastic leukemia in accordance with French-American-British criteria and under immunophenotypical classification and paired within the risk-classification group.
- •Patients with ≥20 kg of weight at the time of treatment assignment.
- •Patients who are able to swallow the medicine
- •Patients agreeing to enter the protocol by the signing of informed consent by the parent
- •Patients who could give their assent to enter the protocol
- •The parent or guardian must be able to read.
排除标准
- •Patients with treatment adherence of ≥80 percent
- •Patients or their parents who decide to abandon the study or who withdraw consent for participation
- •Patients who present grade III or higher adverse event.
- •Patients previously treated with chemotherapy and/or radiotherapy
- •History of peptic acid disease or gastrointestinal bleeding
- •Known pentoxifylline intolerance and general intolerance to xanthine, caffeine or theophylline
- •Patients in treatment with anticoagulants, Cimetidine, Ciprofloxacin, or Theophylline
- •Patients with Down syndrome
- •Patients with several bleeding or extensive retinal hemorrhage, several cardiac arrhythmias (paroxysmal supraventricular tachycardia, congenital atrioventricular block, arrhythmias associated with congenital heart disease, digital poisoning, and patients after cardiac surgery, hypoxia, hypercapnia, and electrolyte disturbances)
- •Patients with hypotension
- •Several liver failures
- •Bleeding diathesis (for bleeding disorders or anticoagulant medication)
研究组 & 干预措施
Pentoxifylline Plus Chemotherapy
Pentoxifylline: 10-20 milligrams per kilogram, doses daily by oral, for 30 days.
Chemotherapy: Prednisone, Vincristine, Daunorubicin, L-asparaginase, Cyclophosphamide, Cytarabine, 6-Mercaptopurine, Methotrexate, Hydrocortisone and Cytarabine
干预措施: Pentoxifylline Plus Chemotherapy (Drug)
Placebo Plus Chemotherapy
Placebo: double blind period, one doses daily for 30 days. Chemotherapy: Prednisone, Vincristine, Daunorubicin, L-asparaginase, Cyclophosphamide, Cytarabine, 6-Mercaptopurine, Methotrexate, Hydrocortisone and Cytarabine
干预措施: Placebo Plus Chemotherapy (Drug)
结局指标
主要结局
Apoptosis measure by Flow Cytometry
时间窗: Up to 28 days after initiation of chemotherapy for remission induction
Percentage of apoptotic cells by Flow Cytometry
次要结局
- Senescence measure by Flow Cytometry(Up to 28 days after initiation of chemotherapy for remission induction.)
- Safety measure by Common Terminology Criteria for Adverse Events version 4.0(Evaluate frequency adverse events with pentoxifylline up to 6 weeks)
研究者
Ramón Óscar González-Ramella, Ph.D
PhD in immunology
University of Guadalajara