A MULTICENTER, PHASE III, OPEN-LABEL,RANDOMIZED STUDY IN PREVIOUSLYUNTREATED PATIENTS WITH ADVANCEDINDOLENT NON-HODGKIN'S LYMPHOMAEVALUATING THE BENEFIT OF GA101(RO5072759) PLUS CHEMOTHERAPYCOMPARED WITH RITUXIMAB PLUSCHEMOTHERAPY FOLLOWED BY GA101 ORRITUXIMAB MAINTENANCE THERAPY INRESPONDERS

• Conditions: PREVIOUSLY UNTREATED PATIENTS WITH ADVANCED INDOLENT NON-HODGKIN'S LYMPHOMA; MedDRA version: 14.1Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-024132-41-IT
• Lead Sponsor: ROCHE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-17
• Last Update Posted: 9 October 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1400

Inclusion Criteria

• Histologically documented,CD20-positive, indolent B-cell NHL consisting of one of the following: follicular lymphoma (Grades 1-3a), splenic MZL, nodal MZL, or extranodal MZL
• Stage III or IV disease, or Stage II bulky disease
• For patients with follicular lymphoma: requirement for treatment, defined as
meeting at least one of the following criteria:
- Bulky disease, defined as a nodal or extranodal (except spleen) mass
=7 cm in the greatest diameter
Local symptoms or compromise of normal organ function due to progressive nodal disease or extranodal tumor mass
Presence of B symptoms (fever, drenching night sweats, or unintentional
weight loss of > 10% of normal body weight over a period of 6 months or less)
- Presence of symptomatic extranodal disease (e.g., pleural effusions,
peritoneal ascites)
- Cytopenias due to underlying lymphoma (i.e., absolute neutrophil count
< 1.0 × 109/L, hemoglobin < 10 g/dL, and/or platelet count < 100 × 109/L)
Involvement of =3 nodal sites, each with a diameter of =3 cm Symptomatic splenic enlargement
• For patients with symptomatic splenic, nodal, or non-gastric extranodal MZL: disease that is de novo or has relapsed following local therapy (i.e., surgery or radiotherapy) and requires therapy, as assessed by the investigator
For patients with symptomatic gastric extranodal MZL:
Helicobacter pylori-negative disease that is de novo or has relapsed following
local therapy (i.e., surgery or radiotherapy) and requires therapy,
as assessed by the investigator, or H. pylori–positive disease that has
remained stable, progressed, or relapsed following antibiotic therapy and
requires therapy, as assessed by the investigator (see Appendix G for
additional details regarding gastric extranodal MZL)
• At least one bi-dimensionally measurable lesion (> 2 cm in its largest
dimension by CT scan or MRI)
In patients with splenic MZL, an enlarged spleen on CT scan or extending
at least 2 cm below the costal margin by physical examination will
constitute measurable disease providing that no explanation other than
lymphomatous involvement is likely. For an enlarged liver to constitute the
only measurable disease parameter, a liver biopsy showing proof of NHL
in the liver is required.
• Able and willing to provide written informed consent and to comply with the
study protocol
• Age =18 years
• ECOG Performance status of 0, 1, or 2 (see Appendix H)
• Adequate hematologic function (unless abnormalities are related to NHL),
defined as follows:
Hemoglobin =9.0 g/dL
Absolute neutrophil count =1.5 x 109/L
Platelet count =75 x 109/L
• For men who are not surgically sterile: agreement to use a barrier method of contraception during the treatment phase and for at least 3 months after the last dose of GA101, rituximab, or bendamustine, or according to institutional guidelines for CHOP or CVP chemotherapy, whichever is longer,and agreement to request that their partners use an additional method ofcontraception, such as oral contraceptives, intrauterine device, barrier method of contraception, or spermicidal jelly
• For women of reproductive potential who are not surgically sterile: agreement to use two adequate methods of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly during the treatment period and for at least 12 months after the last dose of GA101 or rituximab, for at least 3 months after the last dose of bendamustine, or according to institu

Exclusion Criteria

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (e.g., pts in whom dosing with rituximab would be contraindicated for safety reasons)
• Known hypersensitivity to any of the study drugs
• Known sensitivity to murine products
• History of sensitivity to mannitol
• Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma
• Grade 3b follicular lymphoma, SLL, or WM
• Ann Arbor Stage I disease
• For patients with follicular lymphoma: prior treatment for NHL by chemotherapy, immunotherapy, or radiotherapy
• For patients with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy
• Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1, unless administered for indications other than NHL at a dose equivalent to = 30 mg/day prednisone
• History of prior malignancy with the exception of curatively treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• For pts who will be receiving CHOP: left ventricular ejection fraction < 50% by MUGA scan or echocardiogram
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 w. prior to the start of Cycle 1
• Vaccination with a live vaccine within 28 days prior to randomization
• Recent major surgery (within 4 w. prior to the start of Cycle 1), other than for diagnosis
• Any of the following abnormal laboratory values (unless these abnormalities are due to underlying lymphoma):
- Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance normal), or calculated creatinine clearance < 40 mL/min (using Cockcroft–Gault formula)
- AST or ALT > 2.5 × ULN
- Total bilirubin > 1.5× ULN (or > 3 × ULN for pts with documented Gilbert’s syndrome)
- INR > 1.5 × ULN in the absence of therapeutic anticoagulation
- PTT > 1.5 × ULN in the absence of a lupus anticoagulant
• Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology). Pts with occult or prior hepatitis B infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. This population will be limited to 50 pts.
• Positive test results for hepatitis C (hepatitis C virus antibody serology testing). Pts positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
• Known history of HIV seropositive status
• Positive test results for human T-lymphotropic 1 (HTLV 1) virus
• Pregnant or lactating
• Life expectancy < 12 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified