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

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

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)

Study Overview

• Status: Unknown
• Conditions: Thalidomide
• Intervention / Treatment: Drug: Thalidomide combined with R-CHOP; Drug: R-CHOP

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 Type: Interventional
• Enrollment (Anticipated): 162
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Cancer Hospital
      • Contact: Fangfang Lv; Phone Number: 18017312613; Email: Lvff80@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Fang-Fang Lv, Fudan University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 22, 2017
• Primary Completion (ANTICIPATED): August 22, 2020
• Study Completion (ANTICIPATED): August 22, 2020

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (ACTUAL): October 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 24, 2017
• Last Update Submitted That Met QC Criteria: October 20, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Thalidomide; R-CHOP; diffuse large B-cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antibiotics, Antineoplastic; Cyclophosphamide; Thalidomide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: FDSCC LYM2017-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No