Non-Hodgkins Lymphoma Clinical Trial
Official title:
An Open-Label, Multi-Center, Phase IB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin (Plus a Single Pre-Treatment Dose of Obinutuzumab) in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Verified date | April 2024 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients. This study includes an additional open-label imaging feasibility sub-study using a tracer in adult participants with relpased/refractory B-cell non-Hodgkin's lymphoma to image CD8+T-cells at baseline and after treatment with glofitamab, including pre-treatment with obinutuzumab.
Status | Active, not recruiting |
Enrollment | 280 |
Est. completion date | September 30, 2026 |
Est. primary completion date | September 30, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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). Note: The expansion part is restricted to relapsed/refractory follicular lymphoma (r/r FL) and relapsed/refractory diffuse large B cell lymphoma (r/r DLBCL)) - 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 |
Country | Name | City | State |
---|---|---|---|
Belgium | UZ Gent | Gent | |
Denmark | Aarhus Universitetshospital Skejby; Blodsygdomme | Aarhus N | |
Denmark | Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT | København Ø | |
Denmark | Odense Universitetshospital; Hæmatologisk Afdeling | Odense C | |
Israel | Hadassah Ein Karem Hospital; Haematology | Jerusalem | |
Israel | Rabin Medical Center-Beilinson Campus;Hematology-Oncology | Petach Tikva | |
Israel | Chaim Sheba Medical Center; Department of Hematology | Ramat-Gan | |
Italy | ASST PAPA GIOVANNI XXIII; Ematologia | Bergamo | Lombardia |
Italy | Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli" | Bologna | Emilia-Romagna |
Italy | Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia | Milano | Lombardia |
Italy | Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica | Napoli | Campania |
Spain | Hospital Duran i Reynals; Servicio de Hematologia | Barcelona | |
Spain | Hospital Universitari Vall d'Hebron; Servicio de Hematologia | Barcelona | |
Spain | START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | |
Spain | Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia | Malaga | |
Spain | Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | |
United Kingdom | The HOPE Clinical Trials Unit | Leicester | |
United Kingdom | University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility | London | |
United Kingdom | The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | |
United States | Novant Health Cancer Institute | Charlotte | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
United States, Belgium, Denmark, Israel, Italy, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose Limiting Toxicities (DLTs) | Atezolizumab Arm: During DLT period of 21 days (or up to 42 days in the case of cycle delay), starting on Day 1, Cycle 2; Polatuzumab Vedotin Arm: During 5-week DLT period starting Cycle 1, Day 8 | ||
Primary | Change in Maximum Standardized Update Value (SUVmax) Based on 89Zr-PET/CT Scans | From baseline to Day 13 | ||
Primary | Change in Peak SUV (SUVpeak) Based on 89Zr-PET/CT Scans | From baseline to Day 13 | ||
Primary | Change in Mean SUV (SUVmean) Based on 89Zr-PET/CT Scans | From baseline to Day 13 | ||
Primary | Change in CD8 Tumor Volume Based on 89Zr-PET/CT | From baseline to Day 13 | ||
Secondary | Percentage of Participants with Adverse Events (AEs) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Anti-Drug Antibody (ADA) Formation | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Complete Response (CR) Rate, as Assessed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Scan | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Objective Response Rate (ORR) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Disease Control Rate (DCR) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Duration of Response (DOR) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Duration of Complete Response | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Time to First Complete Response (TFCR) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Time to First Overall Response (TFOR) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Progression-Free Survival (PFS) | Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression) | ||
Secondary | Overall Survival (OS) | Baseline through end of survival follow-up phase (survival follow-up is every 3 months until death, lost to follow-up, withdrawal of consent, or study termination) | ||
Secondary | Elimination Half-Life (T1/2) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Area Under the Concentration-Time Curve (AUC) for Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Time to Maximum Observed Serum Concentration (Tmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Maximum Observed Serum Concentration (Cmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Minimum Serum Concentration (Cmin) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Clearance (CL) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | Volume of Distribution at Steady-State (Vss) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin | At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) | ||
Secondary | CD8-Positive T Cell Proliferation | At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) | ||
Secondary | CD20-Positive B-Cell Reduction | At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) | ||
Secondary | SUVmax of 89Zr-Df-IAB22M2C | From baseline to Day 13 | ||
Secondary | SUVpeak of 89Zr-Df-IAB22M2C | From baseline to Day 13 | ||
Secondary | SUVmean of 89Zr-Df-IAB22M2C | From baseline to Day 13 | ||
Secondary | Tumor Volume Based on 89Zr-Df-IAB22M2C PET-uptake | From baseline to Day 13 | ||
Secondary | Quantitation of CD8+ Cells on Biopsy Samples | From baseline to Day 13 |
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