Status:

RECRUITING

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

Lead Sponsor:

University College, London

Collaborating Sponsors:

Hoffmann-La Roche

Conditions:

Large B-cell Lymphoma

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief 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...

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 o...

Eligibility Criteria

Inclusion

  • Histologically proven CD20+ LBCL (with CD20 positivity at any timepoint) including diffuse large B cell lymphoma, high grade B cell lymphoma with MYC, BCL2 and/or BCL6 (double/triple hit lymphoma), high grade B cell lymphoma not otherwise specified (NOS), primary mediastinal B-cell lymphoma or transformed follicular lymphoma.
  • 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

  • Patients with known active infection
  • 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

Key Trial Info

Start Date :

August 16 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

July 30 2028

Estimated Enrollment :

99 Patients enrolled

Trial Details

Trial ID

NCT06071871

Start Date

August 16 2024

End Date

July 30 2028

Last Update

December 24 2024

Active Locations (5)

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Page 1 of 2 (5 locations)

1

Kings College Hospital NHS Foundation Trust

London, United Kingdom

2

University College London Hospitals NHS Foundation Trust

London, United Kingdom

3

The Christie NHS Foundation Trust

Manchester, United Kingdom

4

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom