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

Sponsor

Fudan University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03318835

Collaborator

(none)

162

Enrollment

Location

Arms

Anticipated Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Thalidomide	Drug: Thalidomide combined with R-CHOP Drug: R-CHOP	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

162 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 22, 2017

Anticipated Primary Completion Date :

Aug 22, 2020

Anticipated Study Completion Date :

Aug 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 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 Other Names: RT-CHOP
Active Comparator: 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	Drug: 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

Arm

Intervention/Treatment

Experimental: 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

Drug: Thalidomide combined with R-CHOP

Other Names:

RT-CHOP

Active Comparator: 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

Drug: 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

Outcome Measures

Primary Outcome Measures

3 year PFS [3 years]
3 year progression free survival

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.