TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

Sponsor

Institute of Hematology & Blood Diseases Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04453345

Collaborator

The First Affiliated Hospital of Nanchang University (Other), First Affiliated Hospital of Guangxi Medical University (Other), Henan Cancer Hospital (Other), The First Hospital of Jilin University (Other), Central South University (Other), Tianjin First Central Hospital (Other)

Enrollment

Locations

Arm

144

Anticipated Duration (Months)

4.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
T-LGL Leukemia Clpd-Nk	Drug: thalidomide + prednisone + methotrexate	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

TPM treatment plan: thalidomide 50-100mg qn + prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week.TPM treatment plan: thalidomide 50-100mg qn + prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Efficacy of Thalidomide Plus Prednisone and Methotrexate for the Symptomatic Large Granular Lymphocytic Leukemia - a Prospective Multicenter Clinical Trial From China

Actual Study Start Date :

May 20, 2013

Anticipated Primary Completion Date :

May 20, 2023

Anticipated Study Completion Date :

May 20, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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. Other Names: TPM regimen

Arm

Intervention/Treatment

Experimental: 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.

Drug: thalidomide + prednisone + methotrexate

Other Names:

TPM regimen

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530000
2	Henan Cancer Hospital	Zhengzhou	Henan	China	450000
3	Tongji hopital, Huazhong University of Science and Technology	Wuhan	Hubei	China	430000
4	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China	410000
5	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330000
6	The First Affiliated Hospital of Jilin University	Ch'ang-ch'un	Jilin	China	130000
7	Xijing Hospital, Air Force Military Medical University	Xi'an	Shanxi	China	710000
8	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin	China	300020
9	Tianjin First Central Hospital	Tianjin	Tianjin	China	300020