NCT06071871

A Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma

A Phase II Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 99 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The PORTAL study will test a new combination of drugs (glofitamab, polatuzumab vedotin and obinutuzumab) in patients with large B-cell lymphoma (LBCL) that has come back (relapsed) or not responded to previous treatment. It will determine how safe and effective the combination of these cancer drugs is in treating LBCL before and after CAR-T cell therapy.

Detailed description

This is a phase 2, open label trial conducted in 2 parts. 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

• Large B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	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).
DRUG	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.
DRUG	Obinutuzumab	Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.

Timeline

• Start date: 2024-08-16
• Primary completion: 2027-07-30
• Completion: 2028-07-30
• First posted: 2023-10-10
• Last updated: 2024-12-24

Locations

5 sites across 1 country: United Kingdom