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) - MAI
- Conditions
- Previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL) who have low-intermediate, high-intermediate, or high-risk disease according to the IPI score and patients with bulky tumor (largest diameter = 7.5 cm) regardless of disease risk according to the IPI.MedDRA version: 8.1Level: LLTClassification code 10012818Term: Diffuse large B-cell lymphoma
- Registration Number
- EUCTR2006-005520-16-HU
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1060
• Written informed consent
• Age = 18 years and < 80 years
• CD20-positive diffuse large B-cell lymphoma (DLBCL) or histologic variants (e.g.,
centroblastic, immuno¬blastic, T-cell/histocyte-rich, anaplastic large B cell, plasmablastic lymphoma, lymphomatoid granulomatosis type) under the WHO
classification
• Low-intermediate, high-intermediate, or high risk disease according to the IPI score and/or bulky disease (largest diameter = 7.5 cm) regardless of IPI score
• No prior therapy for DLBCL
• Bi-dimensionally measurable disease (measurable by CT scan or MRI)
• Performance status (ECOG) 0-2
• Cardiac ejection fraction = 50 % as measured by MUGA or 2D-ECHO without clinically significant abnormalities
• Adequate hematological function: hemoglobin = 9g/dL absolute neutrophil count = 1,500/µL and platelet count = 100,000/µL, unless abnormalities are due to bone marrow involvement by lymphoma
• Adequate renal function as documented by:
• a serum creatinine level < 2 mg/dL (177 µmol/L)
• urine dipstick for proteinuria < 2+. If urine dipstick is = 2+, 24-hrs urine collection must demonstrate = 1 g protein secretion in 24 hours
• Adequate hepatic function (total bilirubin < 1.5 x ULN, transaminases [AST and ALT]
< 2.5 x ULN [or < 5 x ULN in the presence of DLBCL involvement of the liver])
• The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or other monitoring test as appropriate, is within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least 2 weeks at the time of randomization. Patients not receiving anticoagulant medication must have an INR = 1.5 and a PTT = 1.5 x ULN within 7 days of randomization.
• Life expectancy > 6 months
• A negative serum pregnancy test one week prior to treatment must be available both for pre-menopausal women and for women who are < 2 years after the onset of menopause, or within 14 days with a confirmatory urine pregnancy test within 1 week prior to study treatment start
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
• Transformed NHL or types of NHL other than DLBCL and its subtypes according to WHO classification
• Prior therapy for DLBCL
• CNS involvement by lymphoma or any evidence of spinal cord compression. Brain
CT/MRI is only mandatory (within 4 weeks prior to randomization) in case of clinical
suspicion of CNS involvement by lymphoma.
• CT-scan based evidence of tumor invading major blood vessels (putting patients at risk for bleeding during study treatment). Lymphoma adjacent to blood vessels are
not excluded.
• Clinical, radiological or endoscopic evidence of lymphoma infiltration of the wall of the esophagus, the stomach or the small and large bowel (endoscopy is not a
mandated pre-study procedure). Lymphoma adjacent to these organ walls are not
excluded.
• Seropositivity for Hepatitis B unless clearly due to vaccination (Hepatitis B testing is not mandatory, but highly recommended)
• Known HIV infection (HIV testing is not mandatory in this study)
• Active viral, bacterial or fungal infection
• History of solid organ transplantation
• Pregnant or nursing females
• Men and women of childbearing potential (< 2 years after last menstruation) not using effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile)
• Prior malignancy (except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, in situ cervical cancer, 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 its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies)
• Uncontrolled seizures requiring permanent anticonvulsant therapy
• Severe chronic obstructive pulmonary disease with hypoxemia
• Uncontrolled diabetes mellitus
• Uncontrolled hypertension, CVA/stroke (= 6 months prior to randomization),
myocardial infarction (= 6 months prior to randomization), unstable angina
(= CCS Grade IV), thrombosis within 6 months before enrolment, NYHA = Grade II
CHF, or serious cardiac arrhythmia requiring ongoing medication
• Clinically significant, active peripheral vascular disease, serious non-healing
wound/ulcer, bone fracture, bleeding diathesis (history or evidence of inherited bleeding diathesis) or coagulopathy
• Major surgery, open biopsy or major trauma within 28 days before enrolment (lymph node
biopsies are not considered major surgery), or the need for major surgery during the course of study treatment
• History of active ulcer (within 1 year prior to randomization), abdominal fistula,
gastrointestinal perforation, or intra-abdominal abscess or concurrent therapy for
treatment/prevention of ulcer (Antacids are allowed for other indications, e.g., gastroesophageal reflux disease, prophylactic medication during immunochemotherapy, etc.).
• Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational therapeutic study
• Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates use of an investigational drug, or patient at high risk from treatment
complications
• Any co-existing medical or psychological condition that would compromise ability to
give informed con
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To demonstrate superior clinical efficacy as measured by progression free survival (PFS) of bevacizumab in combination with rituximab and CHOP (RA-CHOP) versus R-CHOP alone for the treatment of previously untreated patients with diffuse large B cell lymphoma (DLBCL) with at least low-intermediate risk disease according to the IPI or bulky disease regardless of IPI risk category.;Secondary Objective: • To compare the overall survival (OS) between both treatment groups.<br>• To compare event-free survival (EFS) between both treatment groups.<br>• To compare disease-free survival (DFS) between both treatment groups<br>• To compare the safety profile of both treatment arms.<br>• To compare the overall response rate (ORR) between both treatment groups.<br>• To compare the complete response rate (CR) between both treatment groups.;Primary end point(s): • Progression free survival (PFS) as assessed by the Investigators
- Secondary Outcome Measures
Name Time Method