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Clinical Trials in Denmark / NCT03533283
Active, not recruiting Phase 1/2

An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

NCT03533283 · tracked via the Priya Life Science Denmark tracker
Phase
Phase 1/2
Started
2018-05-08
Last updated
2026-07-06

Condition(s) studied

Non-Hodgkins Lymphoma

Investigational drug(s) / intervention(s)

Glofitamab →Atezolizumab →Obinutuzumab →Tocilizumab →Polatuzumab Vedotin →89Zr-Df-IAB22M2C

Glofitamab: Glofitamab will be administered through IV infusion every 3 weeks (Q3W) beginning Cycle 1, Day 1, for up to 17 cycles (Cycle = 21 days). Step-up dosing, in which an initial lower dose will be followed by a higher dose 1 week later, will be considered for the initial treatment phase and for Cycle 9 of the re-treatment phase.

Atezolizumab: Atezolizumab will be administered in combination with Glofitamab through IV infusion Q3W from Cycle 2, Day 1, for up to 16 cycles (Cycle = 21 days).

Obinutuzumab: Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.

Tocilizumab: Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).

Polatuzumab Vedotin: Polatuzumab vedotin will be administered in combination with Glofitamab (on different days) Q3W from Cycle 1, Day 2, for up to 12 cycles (Cycle = 21 days).

89Zr-Df-IAB22M2C: Participants will receive 89Zr-Df-IAB22M2C (Cycle 1 only) prior to obinutuzumab pre-treatment and again on Day 10 after dosing with glofitamab, followed by PET/CT.

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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

Primary outcome measure(s)

Trial sites (19)

FacilityCityRegionStatus
UZ Gent Ghent Belgium
Aarhus Universitetshospital Skejby Aarhus N Denmark
Rigshospitalet København Ø Denmark
Odense Universitetshospital Odense C Denmark
Hadassah Ein Karem Hospital Jerusalem Israel
Rabin Medical Center-Beilinson Campus Petah Tikva Israel
Chaim Sheba Medical Center Ramat Gan Israel
Istituto Nazionale Tumori Irccs Fondazione g. Pascale Naples Campania
Policlinico S.Orsola-Malpighi Bologna Emilia-Romagna
Asst Papa Giovanni Xxiii Bergamo Lombardy
Fond. IRCCS Istituto Nazionale Tumori Milan Lombardy
Hospital Universitari Vall d'Hebron Barcelona Spain
Hospital Duran i Reynals Barcelona Spain
START Madrid-FJD, Hospital Fundacion Jimenez Diaz Madrid Spain
Hospital Clinico Universitario Virgen de la Victoria Málaga Spain
Hospital Clinico Universitario de Valencia Valencia Spain
The HOPE Clinical Trials Unit Leicester United Kingdom
University College London Hospitals NHS Foundation Trust London United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom

On this site

📄 Tecentriq (atezolizumab) drug profile → 📄 Actemra (tocilizumab) drug profile →

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03533283 on ClinicalTrials.gov ↗ ← All trials in Denmark