A multi-center, randomized, double-blind, placebo-controlled phase III trial omparing the efficacy of bevacizumab in combination with rituximab and CHOP (RA-CHOP) versus rituximab and CHOP (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL)

Not Applicable

Completed

• Conditions: -C83 Non-follicular lymphoma; Non-follicular lymphoma; C83

• Registration Number: PER-003-08
• Lead Sponsor: F. HOFFMANN-LA ROCHE LTD.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-07
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: Not specified
• Target Recruitment: 29

Inclusion Criteria

• Written informed consent
• Age> 18 years
• Diffuse large CD20 positive B-cell lymphoma (DLBCL) or histological variants according to the WHO classification Low-to-intermediate, high to intermediate or high risk according to the IPI score and / or bulky tumors (diameter) greater than> 7.5 cm) regardless of the IPI score
• Two-dimensionally measurable disease
• Degree of activity (ECOG) O to 2
• Cardiac ejection fraction> 50% as measured by MUGA or 2D-ECH0 without clinically significant abnormalities
• Adequate haematological function: hemoglobin> 9g / dL absolute neutrophil count> 1,500 / pL and platelet count> 100,000 / uL, unless the abnormalities are due to the lymphoma affecting the bone marrow
• Adequate renal function as documented by: a serum creatinine concentration <2 mg / dL (177 pmol / L) urine dipstick for proteinuria <2+. If the urine dipstick is ^ 2+, the 24-hour urine collection should show <1 g of protein secretion
• Adequate liver function (total bilirubin <1.5 X ULN, transaminases <2.5 x ULN [or <5 X ULN in the presence of DLBCL with hepatic involvement])
• The use of oral or parenteral anticoagulants at full doses is permitted as long as the INR or other monitoring test is adequate, within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least 2 weeks after of the moment of randomization. Patients who do not receive anticoagulants should have an INR <1.5 and an aPTT <1.5 X ULN within 7 days of randomization.
• Life expectancy> 6 months
• You must have a negative pregnancy test one week before treatment for both premenopausal women and women <2 years after the onset of menopause or within 14 days with a confirmatory urine pregnancy test within a period of 1 week before the start of the study treatment

Exclusion Criteria

• NHL transformed or NHL types other than: DLBCL and its subtypes according to the WHO classification
• Pre-treatment for DLBCL
• CNS involvement due to lymphoma or any evidence of compression of the spine. CT / MRI of the brain is only mandatory (within 4 weeks before randomization) in case of clinical suspicion of CNS involvement due to lymphoma.
• Evidence of invasion of the tumor by CT of the main blood vessels (which puts the patient at risk of bleeding during the study treatment)
• Affectation of the digestive system due to lymphoma. Note that endoscopy is not a mandatory procedure prior to the study for all patients.
• Seopositivity for Hepatitis B unless it is clearly due to the vaccine (the Hepatitis B test is not mandatory, but is highly recommended)
• Knowledge of HIV infection (the HIV test is not mandatory in this study)
• Active viral, bacterial or fungal infection
• History of solid organ transplantation
• Pregnancy or lactating women
• Men and women of childbearing age (<2 years after the last menstrual period) who do not use effective means of contraception (oral contraceptives, intrauterine device, barrier method of contraception together with spermicidal jelly or surgical sterilization)
• Previous malignant tumor (except basal cell carcinoma treated properly, cervical cancer in situ or any other cancer for which the patient has been in remission for at least 5 years)
• Known hypersensitivity to any of the study drugs or their ingredients {i.e., hypersensitivity to Polysorbate 20, products of CHO cells or recombinant human antibodies)
• Uncontrolled seizures requiring permanent anticonvulsant therapy
• Severe chronic obstructive pneumopathy with hypoxemia
• Uncontrolled diabetes mellitus
• Uncontrolled hypertension, CVA / stroke (<6 months before randomization), myocardial infarction (<6 months before randomization), unstable angina (> NYHA Grade IV), thrombosis within 6 months before enrollment , CHF> NYHA Grade II, or severe cardiac arrhythmia that requires ongoing treatment
• Clinically significant active peripheral vascular disease, serious wound / ulcer that does not heal, bone fracture, bleeding diathesis (history or evidence of hereditary bleeding diathesis) or coagulopathy
• Major surgery, open biopsy or trauma within 28 days before enrollment (lymph node biopsies are not considered major surgery), or the need for major surgery during the course of the study treatment
• History of active ulcer (within 1 year before randomization), abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess or simultaneous treatment for ulcer treatment / prevention
• Current or recent treatment (within 30 days prior to the start of study treatment with another investigational medication) or participation in another therapeutic research study
• Evidence of any other disease, metabolic insufficiency, finding on physical examination or clinical laboratory findings that of a reasonable suspicion of a disease or condition that contraindicates the use of a research drug, or patient at high risk of treatment complications
• Any coexisting medical or physiological condition that could compromise the ability to provide informed consent

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:PFS is measured as the time from the date of randomization to the date of disease progression / relapse or death.<br>Measure:Efficacy in terms of survival without progression<br>Timepoints:After the study<br>