TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

NCT04453345 | Unknown Phase 2 DMC

• 1 other identifier: IIT2020003-EC-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 9

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.

Conditions

T-LGL Leukemia; Clpd-Nk

Keywords

Large granular lymphocyte leukemia; thalidomide; methotrexate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall response (PR)

  From date of TPM treatment until the date of at least partial response, assessed up to 100 months

• 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

• 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

Study Arms (1)

TPM regimen

EXPERIMENTAL

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

Interventions

thalidomide + prednisone + methotrexate DRUG

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.

Also known as: TPM regimen

TPM regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• The First Affiliated Hospital of Nanchang University: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator
• Henan Cancer Hospital: collaborator
• The First Hospital of Jilin University: collaborator
• Central South University: collaborator
• Tianjin First Central Hospital: collaborator

Study Sites (9)

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Tongji hopital, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

RECRUITING

The First Affiliated Hospital of Jilin University

Ch’ang-ch’un, Jilin, 130000, China

RECRUITING

Xijing Hospital, Air Force Military Medical University

Xi’an, Shanxi, 710000, China

RECRUITING

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Tianjin First Central Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (7)

• 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. No abstract available.

  PMID: 27055870 BACKGROUND

• 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.

  PMID: 28128670 BACKGROUND

• 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.

  PMID: 30231346 BACKGROUND

• 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.

  PMID: 24778993 BACKGROUND

• 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.

  PMID: 32062772 BACKGROUND

• 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.

  PMID: 28115367 BACKGROUND

• Yu Y, Li Y, Cui R, Yan Y, Li F, Chen Y, Wang T, Hu X, Feng Y, Yu T, Huang Y, Sun J, Lyu R, Xiong W, Wang Q, Liu W, An G, Sui W, Xu Y, Huang W, Zou D, Wang H, Xiao Z, Wang J, Qiu L, Yi S. Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study. Signal Transduct Target Ther. 2025 Mar 12;10(1):85. doi: 10.1038/s41392-025-02164-4.

  PMID: 40069155 DERIVED

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic

Interventions

Thalidomide; Prednisone; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• Lugui Qiu

  Blood Disease Hospital, CAMS and Peking Union Medical College

  STUDY DIRECTOR

Central Study Contacts

Shuo Chen

CONTACT

+86022-23909095; chenshuo@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

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

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: July 1, 2020
• Study Start: May 20, 2013
• Primary Completion: May 20, 2023
• Study Completion: May 20, 2025
• Last Updated: July 1, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)