Combination of drugs for treating relapsed large B-cell lymphoma before and after CAR-T therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This trial evaluates the safety and effectiveness of a combination of three drugs—glofitamab, polatuzumab vedotin, and obinutuzumab—in patients with relapsed or refractory large B-cell lymphoma (LBCL). The study is divided into two parts: the first part assesses the efficacy of the drug combination as a bridging treatment to CAR-T cell therapy, while the second part focuses on patients who have not achieved complete metabolic response after CAR-T therapy. Patients will receive multiple cycles of treatment, with their responses monitored through PET-CT scans. The trial aims to improve outcomes for patients who have limited treatment options.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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 Criteria:

* 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

Where it's running

• Kings College Hospital NHS Foundation Trust
  London, United Kingdom Recruiting
• University College London Hospitals NHS Foundation Trust
  London, United Kingdom Recruiting
• The Christie NHS Foundation Trust
  Manchester, United Kingdom Recruiting
• Nottingham University Hospitals NHS Trust
  Nottingham, United Kingdom Recruiting
• Churchill Hospital
  Oxford, United Kingdom Recruiting

Study contacts

• Principal investigator: William Townsend — University College London Hospitals
• Study coordinator: PORTAL Trial Manager
• Email: ctc.portal@ucl.ac.uk
• Phone: 020 7679 9860

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Using BHB with CAR-T therapy for lymphoma treatment

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• In Vivo CD19/CD20 CAR T-Cell Therapy for Relapsed or Refractory B-Cell Lymphoma

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• Glofit-GemOx Bridging to Liso-cel for Relapsed/Refractory Large B-Cell Lymphoma

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• Pola-ZR-Glo for older patients with large B‑cell lymphoma

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.