A Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma
NCT ID: NCT06071871
Last Updated: 2024-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
99 participants
INTERVENTIONAL
2024-08-16
2028-07-30
Brief Summary
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Detailed Description
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The overall aim is:
Part 1: To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with relapsed or refractory large B cell lymphomas.
Part 2: To determine the efficacy of Pola-Glofit in patients with relapsed or refractory large B cell lymphomas who have failed to achieve CMR, or progressed after CAR-T cell therapy.
Treatment consists of:
Part 1: Patients will receive 2 cycles of Pola-Glofit. Obinutuzumab is given 7 days before the first dose of Glofit. After 2 cycles, patients have a PET-CT scan to check the response. If the scan shows a response and the patient is still suitable for CAR-T, patients will receive planned CAR-T therapy. If the patient is not suitable to continue with CAR-T, patients can receive up to 4 more cycles of Pola-Glofit, and then 6 cycles of Glofit.
Part 2: Patients will receive 6 cycles of Pola-Glofit, and then 6 cycles of Glofit. Obinutuzumab is given 7 days before the first dose of Glofit.
For both Part 1 and Part 2, all cycles are 21 days. A step-up dosing regimen will be followed:
* Cycle 1 Day 1: Obinutuzumab is given intravenously at a dose of 1g over 4-5 hours.
* Cycle 1 Day 2: Polatuzumab is given intravenously at a dose of 1.8mg/kg over 90 minutes.
* Cycle 1 Day 8: Glofitamab is given intravenously at a dose of 2.5mg over 4 hours. Patients need to stay in hospital for 24 hours.
* Cycle 1 Day 15: Glofitamab is given intravenously at a dose of 10mg over 2 hours. (Patients may need to stay in hospital for 24 hours.)
* From Cycle 2-6, Polatuzumab is given intravenously at a dose of 1.8mg/kg over 30 minutes on Day 1, and Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1.
* From Cycle 7-12, Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1.
Patients will be followed up until the last patient completes their 1 year post-treatment follow up visit.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Part 1
Patients whose large B-cell lymphoma has progressed/not responded to previous treatment and are due to start standard CAR-T therapy.
All patients receive 2 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola). Obinutuzumab pre-treatment is given on cycle 1 day 1.
Patients have a PET-CT scan to check the response after cycle 2. If the scan shows a response and patients are still suitable for CAR-T cell therapy, patients will proceed to receive planned CAR-T therapy and will not receive further Glofit-Pola in Part 1. If not, patients can receive 4 more cycles of glofitamab and polatuzumab vedotin, and then 6 cycles of glofitamab.
Glofitamab
Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8. Patients need to stay in hospital for 24 hours.
Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15. (Patients may need to stay in hospital for 24 hours.) Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-12 (as relevant).
Polatuzumab vedotin
Polatuzumab is given intravenously at a dose of 1.8mg/kg on Cycle 1 Day 2, and then Day 1 of Cycle 2-Cycle 6.
Obinutuzumab
Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.
Part 2
Patients whose large B-cell lymphoma has progressed/not responded after standard CAR-T cell therapy.
All patients receive 6 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola), and then 6 cycles of glofitamab alone. Obinutuzumab pre-treatment is given on cycle 1 day 1.
Glofitamab
Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8. Patients need to stay in hospital for 24 hours.
Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15. (Patients may need to stay in hospital for 24 hours.) Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-12 (as relevant).
Polatuzumab vedotin
Polatuzumab is given intravenously at a dose of 1.8mg/kg on Cycle 1 Day 2, and then Day 1 of Cycle 2-Cycle 6.
Obinutuzumab
Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.
Interventions
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Glofitamab
Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8. Patients need to stay in hospital for 24 hours.
Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15. (Patients may need to stay in hospital for 24 hours.) Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-12 (as relevant).
Polatuzumab vedotin
Polatuzumab is given intravenously at a dose of 1.8mg/kg on Cycle 1 Day 2, and then Day 1 of Cycle 2-Cycle 6.
Obinutuzumab
Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Part 1: Relapsed or refractory disease and eligible for CAR T-cell therapy in the UK and in need of systemic bridging in the opinion of the local investigator.
* Part 2: Failed to achieve CMR (Deauville score 1-3) on PET scan 1-month post CAR-T or progressed at any point post CAR-T (patients in part 2 may have been previously enrolled in Part 1 and responded to Pola-Glofit bridging or be de novo patients who are naïve to this combination)
* At least one measurable target lesion
* Patient has recent archival biopsy tissue available or is willing to undergo a new biopsy.
* ECOG performance status:
* Part 1: ECOG PS 0/1
* Part 2: ECOG PS 0-2
* Life expectancy of ≥ 12 weeks
* Adequate haematological status.
* Adequate liver and renal function
* Negative test for hepatitis B, hepatitis C, HIV and SARS-CoV-2
Exclusion Criteria
* Current ≥ Grade 2 peripheral neuropathy
* History of confirmed progressive multifocal leukoencephalopathy
* Current evidence of CNS lymphoma
* Patients with another invasive malignancy in the last 2 years
* Significant history of cardiovascular disease
* Active autoimmune disease or immune deficiency
* Severe neurological disorder
* Uncontrolled tumour-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites
* Treatment with other standard anti-cancer radiotherapy/chemotherapy including investigational therapy and targeted therapy within 4 weeks prior to cycle 1 day 1
* Prior solid organ transplantation
* Prior allogeneic stem cell transplant
* Autologous SCT within 100 days prior to cycle 1 day 1
* Any history of immune related ≥ Grade 3 adverse events
* Ongoing corticosteroid use \> 25 mg/day of prednisone or equivalent within 4 weeks prior to study treatment
* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
* Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1 day 1
* History of severe allergic anaphylactic reactions to chimeric or humanised monoclonal antibodies or recombinant antibody-related fusion proteins.
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the obinutuzumab, polatuzumab vedotin and/or glofitamab formulation.
* Known or suspected history of HLH
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
University College, London
OTHER
Responsible Party
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Principal Investigators
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William Townsend
Role: PRINCIPAL_INVESTIGATOR
University College London Hospitals
Locations
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Kings College Hospital NHS Foundation Trust
London, , United Kingdom
University College London Hospitals NHS Foundation Trust
London, , United Kingdom
The Christie NHS Foundation Trust
Manchester, , United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Countries
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Central Contacts
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Other Identifiers
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2022-003727-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
UCL/150862
Identifier Type: -
Identifier Source: org_study_id