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

Phase 3

• Conditions: Thalidomide
• Interventions: Drug: Thalidomide combined with R-CHOP; Drug: R-CHOP

• Registration Number: NCT03318835
• Lead Sponsor: Fudan University

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-08-22
• Status Verified: 2017-10
• Study First Submitted: 2017-10-11
• Study First Submitted QC: 2017-10-20
• Last Update Submitted: 2017-10-20
• Study First Posted: 2017-10-24
• Last Update Posted: 2017-10-24
• Primary Completion: 2020-08-22
• Study Completion: 2020-08-22

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

1. Age range ≥18 years old
2. Eastern Cooperative Oncology Group performance status 0 to 2;
3. Newly diagnosed, untreated, histological confirmed diffuse large B cell lymphoma, non-GCB subtype, and Myc≥40% as well as Bcl-2≥70% through immunohistochemistry；
4. Measurable disease was defined as at least one lesion ≥1.5 cm in length-diameter and ≥0.5 cm in short-diameter by CT.
5. Patients have written informed consent to participate in the study.
6. Ultrasonic cardiogram showed left ventricle ejection fraction ≥ 50%, EKG showed on signs of myocardial ischemia, with no previous arrhythmia which need pharmacological intervention.
7. White blood cell ≥ 3.5×109/L, absolute neutrophil count ≥ 1.5×109/L，platelet ≥ 80×109/L，hemoglobin ≥ 90 g/L
8. total bilirubin < 1.5×upper limit of normal(ULN), ALT and AST < 1.5× ULN
9. serum creatine <1.5×ULN, and creatinine clearance rate (CCR) ≥ 30 ml/min

Exclusion Criteria

1. Presence of CNS involvement
2. Particular kind of DLBCL，such as primary mediastinal/thymic B-cell lymphoma, elderly EBV positive DLBCL, primary cutaneous large B lymphoma.
3. History of myocardial diseases, such as congenital heart disease, pericardial disease, heart failure, myocardial infarction, coronary heart disease, valvular heart disease, myocardosis, arrhythmia.
4. History of severe chronic cutaneous diseases.
5. History of allergic asthma or severe allergic diseases.
6. Uncontrolled hypertension and diabetes.
7. History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
8. HIV, HCV, or syphilis infection；
9. Presence of active HBV infection（HBV-DNA≥104）；
10. Pregnant or lactating women
11. Previously received organ transplant
12. Having usage of Thalidomide；
13. History of deep vein thrombosis
14. Serious uncontrolled infection
15. Having contraindications to the use of large doses of hormone, such as uncontrolled hyperglycemia, gastric ulcer, mental disorder.
16. Severe neurol of mental illness, including dementia and epilepsy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Thalidomide combined with R-CHOP	Thalidomide combined with R-CHOP	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
R-CHOP	R-CHOP	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

Primary Outcome Measures

Name	Time	Method
3 year PFS	3 years	3 year progression free survival

Secondary Outcome Measures

Name	Time	Method
ORR	6 weeks，12 weeks，18weeks	overall response rate
OS	3 years	overall survival
adverse event	throughout the treatment period，up to 6 months	adverse event related to treatment

Trial Locations

Locations (1)

Fudan University Cancer Hospital; 🇨🇳 Shanghai, Shanghai, China