Relapsed/Refractory Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM) MedDRA version: 20.0 Level: LLT Classification code 10054697 Term: Waldenstrom's macroglobulinemia recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10054698 Term: Waldenstrom's macroglobulinemia refractory System Organ Class: 10029104 - Neoplasms benign, malignant and u
Conditions
Interventions
Product Name: Atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44
Current Sponsor code: RO5541267
Other descriptive
Sponsors
Roche Farma S.A. (Soc.unipersonal)que realiza el ensayo en España y que actúa como representante de F.Hoffmann- La Roche
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Ability to comply with the protocol - Age >= 18 years - Histologically documented, CD20 positive non-Hodgkin lymphoma (NHL), relapsed or refractory MCL and MZL. For WM relapse/refractory intended as reappearance of monoclonal IgM protein and/or recurrence of bone marrow involvement, lymphadenopathy/splenomegaly or symptoms attributable to active disease Patients must have failed at least 1 prior line of systemic treatment for mucosa associated lymphoid tissue patients. - Bone marrow biopsy and/or other sites of disease at screening for tumor staging and response evaluation - ECOG performance status of 0, 1 or 2 - Life expectancy>=12 weeks - For mantle cell lymphoma (MCL) and nodal marginal zone lymphoma (MZL), at least one bi-dimensionally measurable lesion>=1.5 cm in its largest dimension by Computed Tomography scan or MRI, as defined by Revised Response Criteria for Malignant Lymphoma - Adequate hematologic and end-organ function - For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use single highly effective or combined contraceptive methods that result in a failure rate of ? 1% per year during the treatment period for at least 18 months after the last dose of combination therapy - For women of childbearing potential, a negative serum pregnancy test result within 7 days prior to commencement of dosing - For men, agreement to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 3 months after the last dose of atezolizumab - Tumor tissue or archival only 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 84
Exclusion criteria
Exclusion criteria: - Any approved anticancer therapy or hormonal therapy within 3 weeks prior to initiation of study treatment. Any radiotherapy within 4 weeks prior to initiation of study treatment. - Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment - Known Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma - Uncontrolled tumor-related pain - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; patients with indwelling catheters are eligible - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab - History of other malignancy - History of severe allergic or anaphylactic or other hypersensitivity reactions to chimeric or humanized or murine monoclonal antibodies or fusion proteins or murine proteins or known sensitivity or allergy to murine products - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization within 4 weeks of the start of Cycle (C) 1 - Regular treatment with corticosteroids within the 4 weeks prior to the start of C1 General Medical Exclusions - Pregnant and lactating women, or intending to become pregnant during the study. Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 7 days prior to Day (D) 1 of C1 - History of autoimmune disease - Other serious underlying medical conditions, which, in the Investigator’s judgment, could impair the ability of the patient to participate in the study - Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina - Patients with history of confirmed progressive multifocal leukoencephalopathy - Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation - History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening - Serum albumin < 2.5 g/dL - Positive test for HIV, human T-lymphotrophic 1 virus, and hepatitis B or C - Active tuberculosis - Received therapeutic oral or IV antibiotics within 4 weeks prior to C1D1 - Major surgical procedure other than for diagnosis within 28 days prior to C1D1 - Administration of a live, attenuated vaccine within 4 weeks before C1D1 Exclusion Criteria Related to Medications - Hypersensitivity to obinutuzumab, rituximab or atezolizumab or their formulation excipients - Prior treatment with obinutuzumab or atezolizumab, or anti progressive disease (PD)-1 or programmed death-ligand 1 (PDL-1) antibodies - Fludarabine or Campath® within 12 months prior to study entry - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to C1D1 - Treatment with systemic immunosuppressive medications wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of atezolizumab in combination with obinutuzumab or rituximab;Secondary Objective: • To evaluate the efficacy of atezolizumab in combination with obinutuzumab or rituximab • To evaluate the safety and tolerability of atezolizumab in combination with obinutuzumab or rituximab • To characterize the pharmacokinetics of atezolizumab and obinutuzumab when administered in combination in MCL and WM patients • To characterize the pharmacokinetics of atezolizumab and rituximab when administered in combination in MZL patients • To evaluate the immune response to atezolizumab with obinutuzumab or rituximab;Primary end point(s): 1. For MCL and nodal and extra-nodal MZL, objective response (OR) at end of Induction, defined as a complete response (CR) or partial response (PR) based on modified Cheson 2007 criteria (excluding PET) 2. For WM, best overall objective response (BOR), defined as a CR, very good partial response, PR, or minimum response, based on Owen 2013 criteria 3. For gastric MZL, OR at end of Induction, defined as a CR or probable minimal residual disease or responding residual disease, based on the histological grading system of GELA 2003 criteria 4. For splenic MZL, OR at end of Induction, defined as a CR or PR based on Matutes (2008);Timepoint(s) of evaluation of this end point: 1, 3 & 4. At the end of induction 2. Up to approximately 54 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival (PFS), defined as the time from enrolment to the first occurrence of PD or death, as determined by the investigator 2. BOR, defined as best response seen throughout study 3. Complete Response Rate defined as best response of CR 4. Duration of objective response, defined for responding patients as the first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first 5. Time to next treatment, defined as the time from the date of enrolment to the start date of the next anti-lymphoma treatment (NALT) or death from any cause 6. Overall survival, defined as the time from the enrolment to death from any cause 7. Event free survival, defined as the time from enrolment to disease progression or relapse, death from any cause, as assessed by the investigator, or initiation of any NALT 8. Disease-free survival, defined as the time from the date of the first occurrence of a documented CR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator, for the subgroup of patients with a BOR of CR 9. Response rates for MCL and nodal/extranodal MZL using the assessment based on FDG-PET scans based on modified Cheson 2007 10. Safety: Incidence, nature and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) 11. Pharmacokinetic parameters of atezolizumab, obinutuzumab, and rituximab 12. Occurrence of anti-drug antibodies of atezolizumab, obinutuzumab, and rituximab;Timepoint(s) of evaluation of this end point: 1-10. Up to approximately 54 months 11. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 (atezolizumab); C1D1, C2D1, C4D1 (obinutuzumab); C1D1, C2D1, C4D1, C8D1 (rituximab), end of treatment (EOT) and at Follow-up 1 (FU1) 12. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 (atezolizumab); C1D1, C4D1 (obinutuzumab); C1D1, C4D1 (rituximab); | — |
Countries
Bosnia and Herzegovina, France, Germany, Greece, Italy, Korea, Republic of, Latvia, Russian Federation, Slovakia, Spain, Switzerland
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed