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TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

Primary Purpose

T-LGL Leukemia, Clpd-Nk

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
thalidomide + prednisone + methotrexate
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-LGL Leukemia focused on measuring Large granular lymphocyte leukemia, thalidomide, methotrexate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Guangxi Medical UniversityRecruiting
  • Henan Cancer HospitalRecruiting
  • Tongji hopital, Huazhong University of Science and TechnologyRecruiting
  • The Second Xiangya Hospital of Central South UniversityRecruiting
  • The First Affiliated Hospital of Nanchang UniversityRecruiting
  • The First Affiliated Hospital of Jilin UniversityRecruiting
  • Xijing Hospital, Air Force Military Medical UniversityRecruiting
  • Institute of Hematology & Blood Diseases HospitalRecruiting
  • Tianjin First Central HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TPM regimen

Arm Description

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.

Outcomes

Primary Outcome Measures

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）

Secondary Outcome Measures

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.
Progression-free survival (PFS)
the length of time during and after the treatment of LGLL
Duration of response (DoR)
the time from response to progression/death (P/D)
overall survival
the length of the patients survival time

Full Information

First Posted
June 24, 2020
Last Updated
June 26, 2020
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT04453345
Brief Title
TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL
Official Title
The Efficacy of Thalidomide Plus Prednisone and Methotrexate for the Symptomatic Large Granular Lymphocytic Leukemia - a Prospective Multicenter Clinical Trial From China
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2013 (Actual)
Primary Completion Date
May 20, 2023 (Anticipated)
Study Completion Date
May 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-LGL Leukemia, Clpd-Nk
Keywords
Large granular lymphocyte leukemia, thalidomide, methotrexate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Model Description
TPM treatment plan: thalidomide 50-100mg qn + prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week.
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TPM regimen
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
thalidomide + prednisone + methotrexate
Other Intervention Name(s)
TPM regimen
Intervention Description
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 Measure Information:
Title
Complete response (CR) rate of TPM regimen
Description
Hb> 120g / L，platelet> 100×109 / L，ANC > 1.5×109 / L），ALC< 4×109 / L，peripheral LGL in normal（< 0.5×109 / L）
Time Frame
From date of TPM treatment until the date of complete response, assessed up to 100 months
Secondary Outcome Measure Information:
Title
Overall response (PR)
Description
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.
Time Frame
From date of TPM treatment until the date of at least partial response, assessed up to 100 months
Title
Progression-free survival (PFS)
Description
the length of time during and after the treatment of LGLL
Time Frame
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
Title
Duration of response (DoR)
Description
the time from response to progression/death (P/D)
Time Frame
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
Title
overall survival
Description
the length of the patients survival time
Time Frame
From date of TPM treatment until the date of death from any cause, assessed up to 180 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shuo Chen
Phone
+86022-23909095
Email
chenshuo@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lugui Qiu
Organizational Affiliation
Blood Disease Hospital, CAMS and Peking Union Medical College
Official's Role
Study Director
Facility Information:
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qiaochuan Li, Dr
Phone
13768411929
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keshu Zhou, Dr
Phone
13674902391
Facility Name
Tongji hopital, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianfeng Zhou, Dr
Phone
13971600192
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongling Peng, Dr
Phone
17612205739
Facility Name
The First Affiliated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Li, Dr
Phone
18920526571
Facility Name
The First Affiliated Hospital of Jilin University
City
Ch'ang-ch'un
State/Province
Jilin
ZIP/Postal Code
130000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fengyan Jin, Dr
Phone
13844989638
Facility Name
Xijing Hospital, Air Force Military Medical University
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiequn Chen, Dr
Phone
13991907320
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shuhua Yi, Dr.
Phone
86-022-23909106
Email
yishuhua@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Lugui Qiu, Dr.
Phone
86-022-23909286
Email
qiulg@ihcams.ac.cn
Facility Name
Tianjin First Central Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Deng, Dr
Phone
13516224562

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27055870
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. No abstract available.
Results Reference
background
PubMed Identifier
28128670
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.
Results Reference
background
PubMed Identifier
30231346
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.
Results Reference
background
PubMed Identifier
24778993
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.
Results Reference
background
PubMed Identifier
32062772
Citation
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.
Results Reference
background
PubMed Identifier
28115367
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.
Results Reference
background

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TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

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