Combination of drugs for treating relapsed large B-cell lymphoma before and after CAR-T therapy
A Phase II Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma
This study is testing a combination of three drugs to see if they can help people with relapsed large B-cell lymphoma feel better before and after CAR-T therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 99 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University College, London Academic / other |
| Drugs / interventions | obinutuzumab, polatuzumab, glofitamab, CAR T, CAR-T, chemotherapy, prednisone |
| Locations | 5 sites (London and 4 other locations) |
| Trial ID | NCT06071871 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include adults with histologically confirmed CD20+ large B-cell lymphoma who are either eligible for CAR-T therapy or have not responded to previous CAR-T treatment.
Not a fit: Patients with non-CD20+ lymphomas or those who are not eligible for CAR-T therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment strategy could enhance the effectiveness of CAR-T therapy and improve survival rates for patients with relapsed large B-cell lymphoma.
How similar studies have performed: Previous studies have shown promising results with similar drug combinations in treating large B-cell lymphoma, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
London and 4 other locations
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.