Thalidomide Combined With R-CHOP in Newly Diagnosed，Untreated Double-expressor Diffuse Large B-Cell Lymphoma Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of Thalidomide combined with R-CHOP(RT-CHOP) in newly diagnosed，untreated double-expressor Diffuse Large B-Cell Lymphoma patients (DLBCL)

Detailed Description
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Double expressor lymphoma is a subtype of diffuse large B-cell lymphoma defined as having increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry. Patients with double-expressor lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of progression and recurrence. The investigators conducted this study to evaluate the efficacy of Thalidomide combined with R-CHOP(RT-CHOP) in newly diagnosed double-expressed, untreated Diffuse Large B-Cell Lymphoma patients (DLBCL). Thalidomide is a kind of glutamate derivatives, which can inhibit angiogenesis by blocking bFGF and VEGF, and it can also modulate the immune system by co-stimulating T cell proliferation. In addition, thalidomide can also inhibit the IKK activity and block the activation of NF-kB. In this open-label, randomized, phase III study, we are aiming to compare Thalidomide combined with R-CHOP(RT-CHOP) and R-CHOP in newly diagnosed double-expressor Diffuse Large B-Cell Lymphoma patients (DLBCL), in order to find a potential promising way to treat this subtype of lymphoma.

Official Title
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An Randomized, Open-label, Phase III Study Comparing Thalidomide Combined With R-CHOP and R-CHOP in Newly Diagnosed Double-expressor Diffuse Large B-Cell Lymphoma Patients

Conditions
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Thalidomide

Intervention / Treatment
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* Drug: Thalidomide combined with R-CHOP
* Drug: R-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range ≥18 years old Eastern Cooperative Oncology Group performance status 0 to 2; Newly diagnosed, untreated, histological confirmed diffuse large B cell lymphoma, non-GCB subtype, and Myc≥40% as well as Bcl-2≥70% through immunohistochemistry； Measurable disease was defined as at least one lesion ≥1.5 cm in length-diameter and ≥0.5 cm in short-diameter by CT. Patients have written informed consent to participate in the study. Ultrasonic cardiogram showed left ventricle ejection fraction ≥ 50%, EKG showed on signs of myocardial ischemia, with no previous arrhythmia which need pharmacological intervention. White blood cell ≥ 3.5×109/L, absolute neutrophil count ≥ 1.5×109/L，platelet ≥ 80×109/L，hemoglobin ≥ 90 g/L total bilirubin < 1.5×upper limit of normal(ULN), ALT and AST < 1.5× ULN serum creatine <1.5×ULN, and creatinine clearance rate (CCR) ≥ 30 ml/min Exclusion Criteria: Presence of CNS involvement Particular kind of DLBCL，such as primary mediastinal/thymic B-cell lymphoma, elderly EBV positive DLBCL, primary cutaneous large B lymphoma. History of myocardial diseases, such as congenital heart disease, pericardial disease, heart failure, myocardial infarction, coronary heart disease, valvular heart disease, myocardosis, arrhythmia. History of severe chronic cutaneous diseases. History of allergic asthma or severe allergic diseases. Uncontrolled hypertension and diabetes. History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix HIV, HCV, or syphilis infection； Presence of active HBV infection（HBV-DNA≥104）； Pregnant or lactating women Previously received organ transplant Having usage of Thalidomide； History of deep vein thrombosis Serious uncontrolled infection Having contraindications to the use of large doses of hormone, such as uncontrolled hyperglycemia, gastric ulcer, mental disorder. Severe neurol of mental illness, including dementia and epilepsy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide combined with R-CHOP<br>rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6 Thalidomide 200mg PO QN D1-21 | Drug: Thalidomide combined with R-CHOP<br>* rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6 Thalidomide 200mg PO QN D1-21<br>* Other names: RT-CHOP;|
| Active Comparator: R-CHOP<br>rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6 | Drug: R-CHOP<br>* rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year PFS | 3 year progression free survival | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | overall response rate | 6 weeks，12 weeks，18weeks | 
| OS | overall survival | 3 years | 
| adverse event | adverse event related to treatment | throughout the treatment period，up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalidomide, R-CHOP, diffuse large B-cell lymphoma