TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

T-LGL Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04453345
• Other study ID #: IIT2020003-EC-1
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 20, 2013
• Est. completion date: May 20, 2025

Study information

• Verified date: June 2020
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Shuo Chen
• Phone: +86022-23909095
• Email: chenshuo[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: May 20, 2025
• Est. primary completion date: May 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clpd-Nk
• Leukemia
• T-LGL Leukemia

Intervention

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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Jilin University	Ch'ang-ch'un	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin
China	Tianjin First Central Hospital	Tianjin	Tianjin
China	Tongji hopital, Huazhong University of Science and Technology	Wuhan	Hubei
China	Xijing Hospital, Air Force Military Medical University	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (7)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital	Central South University, First Affiliated Hospital of Guangxi Medical University, First Hospital of Jilin University, Henan Cancer Hospital, The First Affiliated Hospital of Nanchang University, Tianjin First Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Cheon H, Dziewulska KH, Moosic KB, Olson KC, Gru AA, Feith DJ, Loughran TP Jr. Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia. Curr Hematol Malig Rep. 2020 Apr;15(2):103-112. doi: 10.1007/s11899-020-00565-6. Review. — View Citation

Dinmohamed AG, Brink M, Visser O, Jongen-Lavrencic M. Population-based analyses among 184 patients diagnosed with large granular lymphocyte leukemia in the Netherlands between 2001 and 2013. Leukemia. 2016 Jun;30(6):1449-51. doi: 10.1038/leu.2016.68. Epub 2016 Apr 8. — View Citation

Lamy T, Moignet A, Loughran TP Jr. LGL leukemia: from pathogenesis to treatment. Blood. 2017 Mar 2;129(9):1082-1094. doi: 10.1182/blood-2016-08-692590. Epub 2017 Jan 23. Review. — View Citation

Matutes E. Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options. Expert Rev Hematol. 2017 Mar;10(3):251-258. doi: 10.1080/17474086.2017.1284585. Epub 2017 Jan 29. Review. — View Citation

Moignet A, Lamy T. Latest Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia. Am Soc Clin Oncol Educ Book. 2018 May 23;38:616-625. doi: 10.1200/EDBK_200689. Review. — View Citation

Zambello R, Teramo A, Gattazzo C, Semenzato G. Are T-LGL Leukemia and NK-Chronic Lymphoproliferative Disorder really two distinct diseases? Transl Med UniSa. 2014 Feb 4;8:4-11. eCollection 2014 Jan. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate of TPM regimen	Hb> 120g / L,platelet> 100×109 / L,ANC > 1.5×109 / L),ALC< 4×109 / L,peripheral LGL in normal(< 0.5×109 / L)	From date of TPM treatment until the date of complete response, assessed up to 100 months
Secondary	Overall response (PR)	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.	From date of TPM treatment until the date of at least partial response, assessed up to 100 months
Secondary	Progression-free survival (PFS)	the length of time during and after the treatment of LGLL	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
Secondary	Duration of response (DoR)	the time from response to progression/death (P/D)	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
Secondary	overall survival	the length of the patients survival time	From date of TPM treatment until the date of death from any cause, assessed up to 180 months