Study on Glofitamab and Atezolizumab or Polatuzumab Vedotin for Adults with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Sponsor: Hoffmann-La Roche
ClinicalTrials ID:NCT03533283
This clinical trial is testing a combination of treatments, including Glofitamab and either Atezolizumab or Polatuzumab Vedotin, to find the best dose and evaluate safety and effectiveness in adults with B-cell Non-Hodgkin's Lymphoma that has returned or not responded to previous treatments.
Patient Parameters
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Program Overview
The study aims to determine the safest and most effective dose of a new combination treatment for adults with B-cell Non-Hodgkin's Lymphoma that has either come back or not responded to other treatments. It will also assess how well the treatment works and its safety. Additionally, the study includes a special imaging sub-study to observe immune cells before and after treatment with Glofitamab, using a tracer to help visualize these cells.
Eligibility Criteria
Main Inclusion Criteria
- Histologically-confirmed hematologic malignancy that is expected to express CD20 (Relapsed after or refractory to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival or patients refusing chemotherapy or autologous stem cell transplant (SCT))
- Dose-escalation: Grades 1-3b relapsed or refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL) (nodal; extra-nodal; or splenic), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (double-hit lymphoma), HGBCL not otherwise specified (NOS), DLBCL arising from FL (transformed FL)
- Dose-expansion: R/R LBCL, including DLBCL NOS, DLBCL arising from FL (transformed FL), PMBCL, HGBCL with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit and triple-hit lymphomas), and HGBCL NOS
- At least one measurable target lesion
- Fresh pre-treatment biopsy, but if this cannot be taken, a previous archived biopsy from metastatic lesion can be taken as replacement if it is not older than 6 months and not confounded by major events (progression, treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function (liver, hematological, renal)
- Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)
Inclusion Criteria Specific to Imaging Substudy
- At least two measurable target lesions
- Able to provide two fresh tumor biopsies (baseline and on-treatment)
Main Exclusion Criteria
- Participants with Chronic Lymphocytic Leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, Richter's transformation, CD20-positive ALL, Burkitt lymphoma, or lymphoplasmacytic lymphoma
- Current > Grade 1 peripheral neuropathy (only for participants being treated in the polatuzumab vedotin arm)
- Patients with known active infection, or reactivation of a latent infection within 4 weeks prior to Obinutuzumab (Gpt) infusion
- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
- History of leptomeningeal disease
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease
- Major surgery or significant traumatic injury </=28 days prior to Gpt infusion
- Significant cardiovascular disease or significant pulmonary disease
- Active or history of autoimmune disease or immune deficiency (with exceptions, e.g. hypothyroidism and Diabetes mellitus Type 1)
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy within 4 weeks prior to Gpt infusion
- Prior solid organ transplantation
- Prior allogenic stem cell transplant (SCT)
- Autologous SCT within 100 days prior to Gpt infusion
- Documented refractoriness to an obinutuzumab-monotherapy regimen
- Prior treatment with anti-cancer/lymphoma therapies and systemic immunotherapeutic/immunostimulating agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to Gpt infusion
- Any history of immune related >/= Grade 3 adverse events (AE) with the exception of endocrinopathy managed with replacement therapy
- Ongoing corticosteroid use >25 milligrams/day of prednisone or equivalent within 4 weeks prior to and during study treatment
- Treatment with systemic immunosuppressive medication
- Administration of a live, attenuated vaccine within 4 weeks prior to Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
Exclusion Criteria Specific to Imaging Substudy
- Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count and/or the presence of abnormal/malignant cells in the peripheral blood differential signifying circulating lymphoma cell
- Participants who have had splenectomy or functional asplenia that could compromise protocol objectives
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Novant Health Cancer Institute | 28204 | Charlotte | North Carolina |
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