Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol Clinical Study in Children 1-19 Years on Maintenance Therapy for Acute Lymphoblastic Leukemia.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- 6-thioguanine (6TG) levels in erythrocytes
研究概览
简要总结
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. The effect on hematological and liver toxicity parameters in blood will also be investigated as well as clinical toxicity.
详细描述
After one month of conventional maintenance therapy (MT) children and adolescents, treated for acute lymphoblastic leukemia on Nordic protocols and with wild type thiopurine methyltransferase (TPMT) are eligible for the study. They will first receive a 12 week phase with normal MT during which time repeated sampling of 6-mercaptopurine (6MP) metabolite levels and other laboratory parameters will be performed. After 12 weeks, allopurinol at a dose of 50 mg/sqm is added (simultaneously reducing the dose of 6MP by 50%) and during the next 12 weeks patients are monitored closely for toxicity and samples for determination of metabolite levels and hematological and liver toxicity are obtained regularly. If, after 4 weeks of allopurinol treatment, the levels of 6-thioguanine are below 200 nmol/mmol hemoglobin, the dose of allopurinol will be increased to 100 mg/sqm. Allopurinol treatment is continued for 12 weeks after which the patients switch to their original maintenance therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of acute lymphoblastic leukemia
- •Treatment according to Nordic Society for pediatric hematology/oncology (NOPHO) ALL2008 based protocols
- •Age 0-18y at time of initial diagnosis
- •TPMT wild type
- •Written informed consent
排除标准
- •Mature B cell lymphoblastic leukemia
- •t(9;22) positive acute lymphoblastic leukemia
- •Unknown TPMT status or presence of TPMT mutation (both heterozygous and homozygous)
- •Known intolerance to any of the chemotherapeutic drugs in the protocol
- •Major organ failure precluding administration of planned chemotherapy
- •Severe liver toxicity defined as persistent (≥ two weeks) elevation of either S-bilirubin > 50 μmol/l or S-GPT > 20 x Upper normal limit (UNL) or P-Prothrombin complex > 1.
- •Reduced kidney function defined as S-creatinine ≥ 1.5 x UNL.
- •Lactating female or female of childbearing potential not using adequate contraception.
研究组 & 干预措施
Standard maintenance therapy
Standard maintenance therapy with 6 mercaptopurine and methotrexate
干预措施: Standard treatment (Drug)
Allopurinol treatment
The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy
干预措施: Allopurinol (Drug)
结局指标
主要结局
6-thioguanine (6TG) levels in erythrocytes
时间窗: Up to week 25
The fraction of patients with 6TG levels over 200 nmol/mmol Hb at week 13 and 25 (ie after 12 weeks standard and allopurinol treatment respectively)
次要结局
- Mean levels of hemoglobin(Up to week 25)
- Mean level of 6-thioguanine(Up to week 25)
- Mean level of 6-methylmercaptopurine (6MMP)(Up to week 25)
- Mean level of DNA-incorporated thioguanine (DNA-TGN)(Up to week 25)
- Mean levels of platelets(Up to week 25)
- Mean levels of absolute neutrophil count (ANC)(Up to week 25)
- Mean levels of white blood cells (WBC)(Up to week 25)
- Glutamate pyruvate transaminase (GPT)(Up to week 25)
- Bilirubin(Up to week 25)
- Hypoglycemia(Up to week 25)
- Metabolic disturbance(Up to week 25)
- Incidence of serious adverse events (SAE)(Up to week 29)
- Cumulative dose of 6-mercaptopurine and methotrexate(Up to week 29)