A Study Exploring the Safety and Efficacy of Atezolizumab Administered in Combination with Obinutuzumab or Rituximab Anti-CD20 Therapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma, Marginal Zone Lymphoma and Waldenström Macroglobulinemia
- Conditions
- Relapsed/Refractory Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM)MedDRA version: 20.0Level: LLTClassification code 10054697Term: Waldenstrom's macroglobulinemia recurrentSystem Organ Class: 100000013195MedDRA version: 20.0Level: LLTClassification code 10054698Term: Waldenstrom's macroglobulinemia refractorySystem Organ Class: 100000013206MedDRA version: 20.0Level: PTClassification code 10077534Term: Marginal zone lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10077533Term: Marginal zone lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003579-22-GR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
- 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
- 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 w
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method