TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL
- Conditions
- Clpd-NkT-LGL Leukemia
- Interventions
- Registration Number
- NCT04453345
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
-
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;
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TPM regimen thalidomide + prednisone + methotrexate 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.
- Primary Outcome Measures
Name Time Method Complete response (CR) rate of TPM regimen 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）
- Secondary Outcome Measures
Name Time Method 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 the length of time during and after the treatment of LGLL
Overall response (PR) From date of TPM treatment until the date of at least partial response, assessed up to 100 months improvement in blood counts (ANC \> 0.5 × 10\^9/L; HGB increased by \>1 g/dL; PLT \> 50 × 10\^9/L), and the absence of required transfusions.
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 the time from response to progression/death (P/D)
overall survival From date of TPM treatment until the date of death from any cause, assessed up to 180 months the length of the patients survival time
Trial Locations
- Locations (9)
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Tongji hopital, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Jilin University
🇨🇳Ch'ang-ch'un, Jilin, China
Institute of Hematology & Blood Diseases Hospital
🇨🇳Tianjin, Tianjin, China
Xijing Hospital, Air Force Military Medical University
🇨🇳Xi'an, Shanxi, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Tianjin First Central Hospital
🇨🇳Tianjin, Tianjin, China