Phase IB: CD20 positive Follicular Lymphoma, WHO grade 1, 2 or 3a relapsed/refractory after =1 prior R-containing regimen Phase II: CD20 positive follicular and agressive B-cell lymphoma (Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma) relapsed/refractory after =1 prior R-containing regimen MedDRA version: 15.0 Level: PT Classification code 10016906 Term: Follicle centre lymphoma, follicular grade I, II, III refractory System Organ Class: 10029104 - Neoplasms benign, malignant and un
Conditions
Interventions
Product Name: Obinutuzumab
Product Code: RO 5072759 / GA101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Current Sponsor code: G
Sponsors
GELARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients Phase II only: patients with either histologically documented CD20-positive Diffuse large-cell lymphoma or Mantle cell lymphoma (cohort 1) or follicular lymphoma, WHO grade 1, 2 or 3a (cohort 2) Phase IB and II: - Relapsed/refractory NHL after =1 prior R-containing regimen with no curative option - Aged 18 years or more - ECOG performance status 0, 1 or 2 - At least one bi-dimensionally measurable nodal or tumor lesion defined by CT scan as: greatest transverse diameter > 1.5 cm and a short axis = 10mm - Signed inform consent - Life expectancy of = 3 months - All subjects must be able to understand and fulfill the lenalidomide Pregnancy Prevention Plan requirements 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 148 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Previous treatment with obinutuzumab or lenalidomide - Known CD20 negative status at relapse/progression. Biopsy at relapse/progression is recommended but not mandatory - Central nervous system or meningeal involvement by lymphoma - Contraindication to any drug contained in the study treatment regimen - Known HIV or HTLV-1 infection, positive serology to HB surface antigen [HBsAg] or total HB core antibody [anti-HB-c]) and Hepatitis C (Hepatitis C virus [HCV] antibody) - Any serious active disease or co-morbid medical condition (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 or other according to investigator’s decision) - Any of the following laboratory abnormalities. o Absolute neutrophil count (ANC) 2.0 mg/dL (34 µmol/L), except if disease related or in case of Gilbert syndrome. - Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min. For phase II part of the study, patients with calculated creatinine clearance between 30 and 50ml/min can be included and lenalidomide dose will be adjusted as follows (10mg once daily). - Prior history of malignancies other than lymphoma unless the subject has been free of the disease for = 5 years - Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form. - Pregnant or lactating females. - Prior = Grade 3 allergic reaction/hypersensitivity to thalidomide. - Prior = Grade 3 rash or any desquamating (blistering) rash while taking thalidomide. - Subjects with = Grade 2 neuropathy. - Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy - Patients taking corticosteroids during 4 weeks before inclusion, unless administered at a dose equivalent to = 10 mg/day prednisone (over these 4 weeks).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase IB: to determine the recommended dose (RD) of lenalinomide (Revlimid) when administered in association with obinutuzumab by escalation approach (3+3 dosing). Phase II: to assess the efficacy of the association of the recommended dose of lenalidomide in combination with obinutuzumab, as measured by the overall response rate (ORR) at the end of 6 cycles in 2 different populations of patients with relapsed/refractory disease: follicular lymphoma and aggressive lymphoma [aNHL] (Diffuse large B-cell and Mantle cell lymphoma). ;Secondary Objective: - To assess the safety of the combination of lenalidomide plus obinutuzumab during induction and maintenance therapy by monitoring all adverse and serious adverse events AEs/SAEs according to the NCICTCAE v. 4. - To assess the efficacy of the combination of lenalidomide plus obinutuzumab: Complete response (CR) rate after 3 and 6 cycles, for patients who received maintenance treatment OR and CR rate at the end of maintenance treatment, best overall response rate (BOR), event free survival (EFS), progression free survival (PFS), response duration (RD) and overall survival (OS).;Primary end point(s): Phase IB: the determination of the recommended dose (RD) of lenalidomide in combination with fixed doses of GA101 by a dose escalation approach (3+3design). Phase II: the efficacy of the recommended dose of lenalidomide in combination with GA101 will be measured by the overall response rate ORR by IWG criteria (Cheson 1999) at the end of 6 cycles in 2 different populations of patients with relapsed/refractory disease: follicular lymphoma and aggressive lymphoma [aNHL] (Diffuse large B-cell and Mantle cell lymphoma);Timepoint(s) of evaluation of this end point: Phase I: at the end of cycle 1 (after 28 days) Phase II: at the end of cycle 6 (after 6 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety of study treatment will be evaluated during induction and maintenance by monitoring all adverse and serious adverse events AEs/SAEs according to the NCI-CTCAE v. 4. - Efficacy will be evaluated by CR rate after 3 and 6 cycles, OR and CR rate at the end of maintenance treatment, BOR, EFS, PFS, RD and OS.;Timepoint(s) of evaluation of this end point: - All adverse events will be reported during the study period up to 28 days after the last drug administration regardless the relationship with study drug and after this period if the event is related to the study drug - after 3 and 6 cycles (after 3 and 6 months) | — |
Countries
Belgium, France
Contacts
Public ContactElise HUTASSE
GELARC
Outcome results
None listed