Clinical trial NCT02428751: R-CHOP Versus R-CDOP as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma
Official title: Rituximab, Cyclophosphamide, Vincristine, and Prednisone in Combination With Doxorubicin (R-CHOP) Versus in Combination With Pegylated-liposomal Doxorubicin (R-CDOP) as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma: a Randomised, Multicentre, Non-inferiority Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma, Large B-Cell, Diffuse
Keywords: Lymphoma, Large B-Cell, Diffuse
liposomal doxorubicin
doxorubicin
event-free survival
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-04-29
Enrollment: 216
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP regimen) has been the first-line chemotherapy for elderly patients with diffuse large B-cell lymphoma (DLBCL). The treatment-related toxicities, especially the severe cardiac toxicities induced by anthracycline drugs (doxorubicin), have become a major concern among elderly patients. Pegylated liposomal doxorubicin is a formulation of doxorubicin with a prolonged circulation time and unique toxicity profile. Previous single arm studies of elderly patients with lymphoma used pegylated liposomal doxorubicin instead of traditional doxorubicin in combination with rituximab, cyclophosphamide, vincristine, and prednisone (the novel R-CDOP regimen), and demonstrated better safety profile, including less bone marrow suppression and less cardiac toxicities, while maintaining the efficacy. However, the efficacy and safety of these two regimens (R-CHOP and R-CDOP) have not been head-to-head compared in a randomized study. The aim of this study is to compare the efficacy and safety of R-CDOP (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated elderly patients with DLBCL.


Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed diagnosis of CD20-positive diffuse large B-cell lymphoma
* 60\~80 years old
* Ann Arbor stage I\~IV
* ECOG physical score of 0\~2
* Have not received previous treatment to lymphoma, including chemotherapy, radiotherapy, or biotherapy
* Have at least one clinically measurable lesion: \>= 2cm under physical examination, or \>= 1.5cm under computed tomography (CT) or magnetic resonance (MR)
* Life expectancy of \>= 3 months
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase and total bilirubin \<= 2 × upper limit of normal (ULN)
* Glomerular filtration rate (MDRD method) \>= 30ml/min
* No abnormalities in blood coagulative function
* Generally normal bone marrow function: while blood cell \>= 3,000/μL, absolute neutrophil count \>= 1,500/μL, hemoglobin \>= 100g/L, platelet \>= 75,000/μL
* No evidence of active hepatitis B or C virus, or human immunodeficiency virus infection
* Left ventricular ejection fraction (LVEF) \>= 45% measured by two dimensional echocardiography or multi-gated acquisition (MUGA) scan
* Cardiac function of class I-II in New York Heart Association (NYHA) classification

Exclusion Criteria:

* Patients with indolent lymphoma
* Positive results for in situ hybridization for Epstein-Barr virus encoded RNA (EBER)
* Serum Epstein-Barr virus DNA \>= 1,000 copies/ml
* Double-hit lymphoma confirmed by fluorescence in situ hybridization (FISH)
* Primary mediastinal B-cell lymphoma
* Involvement of central nervous system
* Bulky disease (\>= 10cm)
* History of cardiac disease, including clinically significant ventricular tachycardia, atrial fibrillation, conduction block, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease which needs medication
* Known allergic reaction to any component of the agents used in the chemotherapeutic regimens that are used in the study
* Previous exposure to anthracycline drugs, rituximab, or chemotherapy for lymphoma
* History of malignant carcinoma within 5 years (except carcinoma in situ of the skin and uterine cervix, and prostatic carcinoma)
* Currently enrolled in other clinical studies
* Other conditions that the investigators consider as inappropriate for enrolling into this study

Primary outcomes:
measure: event-free survival (EFS)
timeFrame: two year
Secondary outcomes:
measure: overall response rate (ORR)
timeFrame: at week 6, 12, 18, and 24 after randomization
measure: complete remission (CR) rate
timeFrame: at week 6, 12, 18, and 24 after randomization
measure: overall survival (OS)
timeFrame: two year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical Unversity
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Wujing Zongdui Hospital of Guangdong Province
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Wen-qi Jiang, M.D.
role: PRINCIPAL_INVESTIGATOR
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