The Efficacy of Thalidomide Plus Prednisone and Methotrexate for the Symptomatic Large Granular Lymphocytic Leukemia - a Prospective Multicenter Clinical Trial From China
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 9
- 主要终点
- Complete response (CR) rate of TPM regimen
研究概览
简要总结
Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disease, with LGL infiltration in peripheral blood and bone marrow, hepatosplenomegaly, and cytopenia. Both T-LGLL and CLPD-NK are indolent disease and share similar biology and clinical course, and treated under the same strategy. So the investigators put them together as LGLL. The investigators used TPM regimen (thalidomide + prednison + methotrexate ) to treat LGLL since 2013, and 18/20 patients (90%) obtained clinical response, including 80% complete response. Adverse events (AE) of grade 3 and above are rare and safe. Therefore, the investigators designed this multicenter clinical trial to validate the efficacy of the TPM regimen in symptomatic T-LGLL and CLPD-NK.
详细描述
Because LGLL has continuously activated cytotoxic T lymphocytes, immunosuppressive therapy is the standard first-line therapy for T-LGLL and CLPD-NK. Previous studies showed that the overall response rate (ORR) of first-line oral immunosuppressants ranged from 21% to 85% (median: 50%). Both methotrexate and cyclosporine A are LGLL first-line treatment options, but the CR rate of methotrexate is only 21%, while the CR rate of CsA is less than 5%. There is insufficient evidence for the treatment of LGLL with prednisone and other glucocorticoids, but it can reduce RA-related inflammation and increase granulocyte levels. The TPM regimen was designed by the investigators. A pilot prospect observation showed that 18/20 (90%) patients obtained response, including 80% CR. This study is a prospective multiple center clinical trail to evaluate the efficacy of TPM regimen in the treatment of symptomatic LGLL. Eligible patients choose the initial treatment plan: thalidomide 50-100mg qn+ prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week. Four months is one course. Maximum three courses will be given if there is a response and thalidomide maintenance will be for another year.
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
- •The gender of the patient is not limited, and the age is ≥18 years old;
- •Must meet diagnostic criteria of T-LGLL or CLPD-NK according to WHO 2016 version;
- •The patient is treatment naive or received single methotrexate less than 4 weeks and without response. If relapsed or refractory patients, the patients must be naive for both thalidomide and methotrexate.
- •With LGLL treatment indications, it mainly includes (meets at least one of the following conditions):
- •ANC <0.5 × 10^9 / L
- •HGB <100g / L or need red blood cell infusion to maintain
- •PLT <50 × 10^9 / L
- •Combining autoimmune diseases that require treatment
- •symptomatic splenomegaly
- •Severe B symptoms
- •Pulmonary hypertension.
- •ECOG performance status score is 0-2;
- •The patient's expected survival time is ≥ 6 months.
排除标准
- •Unable to understand or follow the research procedure;
- •Co-occurrent malignant tumors that has to be treated or course the symptom;
- •Other serious diseases, such as liver, kidney, heart, lung, nerve or metabolic diseases, may impede the ability of patients to tolerate methotrexate, cyclophosphamide or cyclosporin A;
- •ALAT / ASAT or alkaline phosphatase> 3 times the normal value;
- •Creatinine clearance <60ml / min;
- •Serological evidence of active infection of HIV, hepatitis C or hepatitis B;
- •Ineffective contraception;
- •Positive pregnancy test;
- •Pregnant women.
研究组 & 干预措施
TPM regimen
thalidomide 50-100mg daily at bedtime + prednisone 0.5mg/kg qod to 1mg/kg qd + methotrexate 10mg/m2 per week. 4 months one cycle, up to 3 cycles. After get partial remission, thalidomide maintenance will continue up to 2 years.
干预措施: thalidomide + prednisone + methotrexate (Drug)
结局指标
主要结局
Complete response (CR) rate of TPM regimen
时间窗: From date of TPM treatment until the date of complete response, assessed up to 100 months
Hb\> 120g / L，platelet\> 100×109 / L，ANC \> 1.5×109 / L），ALC\< 4×109 / L，peripheral LGL in normal（\< 0.5×109 / L）
次要结局
- Progression-free survival (PFS)(From date of TPM treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Overall response (PR)(From date of TPM treatment until the date of at least partial response, assessed up to 100 months)
- Duration of response (DoR)(From date of getting response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- overall survival(From date of TPM treatment until the date of death from any cause, assessed up to 180 months)
研究者
Yi Shuhua
principal investigator
Institute of Hematology & Blood Diseases Hospital, China