TPM Regimen (Thalidomide, Prednisone and Methotrexate) in LGLL

June 26, 2020 updated by: Yi Shuhua, Institute of Hematology & Blood Diseases Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Contact:
          • Qiaochuan Li, Dr
          • Phone Number: 13768411929
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
          • Keshu Zhou, Dr
          • Phone Number: 13674902391
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Tongji hopital, Huazhong University of Science and Technology
        • Contact:
          • Jianfeng Zhou, Dr
          • Phone Number: 13971600192
    • Hunan
      • Changsha, Hunan, China, 410000
        • Recruiting
        • The Second Xiangya Hospital Of Central South University
        • Contact:
          • Hongling Peng, Dr
          • Phone Number: 17612205739
    • Jiangxi
      • Nanchang, Jiangxi, China, 330000
        • Recruiting
        • The First Affiliated Hospital of Nanchang University
        • Contact:
          • Fei Li, Dr
          • Phone Number: 18920526571
    • Jilin
      • Ch'ang-ch'un, Jilin, China, 130000
        • Recruiting
        • The first Affiliated Hospital of Jilin University
        • Contact:
          • Fengyan Jin, Dr
          • Phone Number: 13844989638
    • Shanxi
      • Xi'an, Shanxi, China, 710000
        • Recruiting
        • Xijing hospital, Air force Military Medical University
        • Contact:
          • Xiequn Chen, Dr
          • Phone Number: 13991907320
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology & Blood Diseases Hospital
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Tianjin First Central Hospital
        • Contact:
          • Qi Deng, Dr
          • Phone Number: 13516224562

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate of TPM regimen
Time Frame: 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）
From date of TPM treatment until the date of complete response, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response (PR)
Time Frame: 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.
From date of TPM treatment until the date of at least partial response, assessed up to 100 months
Progression-free survival (PFS)
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
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
Duration of response (DoR)
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
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
overall survival
Time Frame: 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
From date of TPM treatment until the date of death from any cause, assessed up to 180 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital

Collaborators

The First Affiliated Hospital of Nanchang University
Henan Cancer Hospital
The First Hospital of Jilin University
Central South University
Tianjin First Central Hospital
First Affiliated Hospital of Guangxi Medical University

Investigators

  • Study Director: Lugui Qiu, Blood Disease Hospital, CAMS and Peking Union Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2013

Primary Completion (Anticipated)

May 20, 2023

Study Completion (Anticipated)

May 20, 2025

Study Registration Dates

First Submitted

June 24, 2020

First Submitted That Met QC Criteria

June 26, 2020

First Posted (Actual)

July 1, 2020

Study Record Updates

Last Update Posted (Actual)

July 1, 2020

Last Update Submitted That Met QC Criteria

June 26, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2020003-EC-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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