Clpd-Nk, T-LGL Leukemia
Conditions
Keywords
Large granular lymphocyte leukemia, thalidomide, methotrexate
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.
Interventions
DRUGthalidomide + 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.
Sponsors
The First Affiliated Hospital of Nanchang University
First Affiliated Hospital of Guangxi Medical University
Henan Cancer Hospital
The First Hospital of Jilin University
Central South University
Tianjin First Central Hospital
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
TPM treatment plan: thalidomide 50-100mg qn + prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The gender of the patient is not limited, and the age is ≥18 years old; 2. Must meet diagnostic criteria of T-LGLL or CLPD-NK according to WHO 2016 version; 3. 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. 4. With LGLL treatment indications, it mainly includes (meets at least one of the following conditions): 1. ANC \<0.5 × 10\^9 / L 2. HGB \<100g / L or need red blood cell infusion to maintain 3. PLT \<50 × 10\^9 / L 4. Combining autoimmune diseases that require treatment 5. symptomatic splenomegaly 6. Severe B symptoms 7. Pulmonary hypertension. 5. ECOG performance status score is 0-2; 6. The patient's expected survival time is ≥ 6 months.
Exclusion criteria
1. Unable to understand or follow the research procedure; 2. Co-occurrent malignant tumors that has to be treated or course the symptom; 3. 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; 4. ALAT / ASAT or alkaline phosphatase\> 3 times the normal value; 5. Creatinine clearance \<60ml / min; 6. Serological evidence of active infection of HIV, hepatitis C or hepatitis B; 7. Ineffective contraception; 8. Positive pregnancy test; 9. Pregnant women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactShuo Chen
Outcome results
None listed