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Large B-cell LymphomaPhase 2PORTALNCT06071871

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

A Phase 2 study testing Glofitamab, Polatuzumab vedotin and Obinutuzumab in people with Large B-cell Lymphoma, run by University College, London at 5 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Large B-cell Lymphoma
What is being tested?
Glofitamab, Polatuzumab vedotin and Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
99 participants
Where
5 sitesUnited Kingdom
Study dates
16 Aug 2024to 30 Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

PORTAL Trial Manager contact

020 7679 9860

ctc.portal@ucl.ac.uk

5 sites in 1 country

United Kingdom5 sites, 5 recruiting

  • Kings College Hospital NHS Foundation Trust

    London

    Recruiting

  • University College London Hospitals NHS Foundation Trust

    London

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester

    Recruiting

  • Nottingham University Hospitals NHS Trust

    Nottingham

    Recruiting

  • Churchill Hospital

    Oxford

    Recruiting

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Being tested
Glofitamab, Polatuzumab vedotin, Obinutuzumab
Keywords
Glofitamab, Polatuzumab vedotin, Obinutuzumab, Bridging therapy, Large B-cell Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GlofitamabDrug

    Also called Columvi

    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 vedotinDrug

    Also called Polivy

    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.

  • ObinutuzumabDrug

    Also called Gazyvaro

    Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.

Study groups in NCT06071871
Study groupRoleWhat they receive
Part 1ExperimentalPatients 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.
Receives: Drug: Glofitamab; Drug: Polatuzumab vedotin; Drug: Obinutuzumab
Part 2ExperimentalPatients 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.
Receives: Drug: Glofitamab; Drug: Polatuzumab vedotin; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Overall Response Rate (ORR) to Pola-Glofit as bridging prior to CAR-T cell infusion

    To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with r/r LBCL.

    ORR i.e. the proportion of patients achieving response (Complete Metabolic Response or Partial Metabolic Response) after Pola-Glofit bridging but prior to CAR-T cell infusion, assessed by central review as per 2014 Lugano Classification. This will be presented as a rate with a 70% confidence interval.

    Measured: At Cycle 2 Day 14-19 (or earlier) (each cycle is 21 days)

  2. Part 2: Progression Free Survival (PFS) at 6 months

    To determine the efficacy of Pola-Glofit in patients with LBCL who have failed to achieve CMR, or progressed after CAR-T cell therapy.

    PFS at 6 months will be analysed using Kaplan-Meier survival analysis, with the rate at 6 months (with 70% CI) presented. The median (if reached) and plot will also be given.

    Measured: From the date of registration at Part 2 until the date of first disease progression or death, whichever comes first, assessed up to 4 years

Secondary outcomes (15)

  1. Part 1: Complete Metabolic Response (CMR) rate to Pola-Glofit as bridging prior to CAR-T cell infusion

    Per Lugano 2014 criteria

    Measured: At Cycle 2 Day 14-19 of bridging treatment (each cycle is 21 days)

  2. Part 1: Overall Survival (OS) and Progression Free Survival (PFS)

    Medians (if reached), rates at 6 months and 1 year and plots will be presented

    Measured: From the date of registration at Part 1 until the date of disease progression or death (PFS), or death (OS). This will be assessed from the date of registration until up to 4 years.

  3. Part 1: Safety and toxicity of Pola-Glofit as bridging therapy

    Assessed by CTCAE criteria v5 and ASTCT 2019 criteria for CRS/ICANS adverse events. Assessed in all patients given at least one dose of study treatment in part 1.

    Measured: From registration and during Part 1 bridging treatment, until end of post-treatment safety reporting window (up to six months after last dose of obinutuzumab, plus a further 35 days after last dose of polatuzumab vedotin or last dose of glofitamab)

  4. Part 1: CAR-T associated toxicity post Pola-Glofit bridging following CAR-T therapy

    Assessed in all patients given at least one dose of study treatment in part 1 and infused. Assessed by CTCAE criteria v5 and ASTCT 2019 criteria for CRS/ICANS adverse events.

    Measured: Between Day 0 and Day 28 following CAR-T therapy

  5. Part 1: Response rate post CAR-T for all infused patients

    Per Lugano 2014 criteria. Response rates at 1, 3 and 6 months post CAR-T therapy.

    Measured: From CAR-T infusion until 6 months post CAR-T therapy

  6. Part 1: Duration of Response (DoR) and Duration of Complete Response (DoCR) for Pola-Glofit and CAR-T

    Response defined as PR (partial response) or better.

    Measured: From the date of first response until disease progression. This will be assessed from the date of registration until up to 4 years.

  7. Part 1: Non-Relapse Mortality (NRM)

    NRM rates at 6 months and 1 year

    Measured: From the date of registration until the date of NRM. This will be assessed from the date of registration until up to 4 years.

  8. Part 2: Complete Metabolic Response (CMR) rate to Pola-Glofit/Glofitamab at any point

    Per Lugano 2014 criteria

    Measured: From the date of registration until up to 4 years

  9. Part 2: Response rate for patients who received Pola-Glofit bridging versus those who have not

    Per Lugano 2014 criteria. Response rates following 2 and 5 cycles of Part 2 treatment.

    Measured: From the date of registration until Cycle 5 (approximately 12 weeks. Each cycle is 21 days).

  10. Part 2: Safety and toxicity of Pola-Glofit post CAR-T therapy

    Assessed by CTCAE criteria v5 and ASTCT 2019 criteria for CRS/ICANS adverse events. Assessed in all patients given at least one dose of study treatment in part 2.

    Measured: Throughout Part 2 treatment until end of post-treatment safety reporting window (up to six months after last dose of obinutuzumab, plus a further 35 days after last dose of polatuzumab vedotin or last dose of glofitamab)

  11. Part 2: Overall Survival (OS)

    Median (if reached), rates at 6 months and 1 year (with 95% CIs) and plots will be presented.

    Measured: From the date of registration for Part 2 until the date of death, assessed up to 4 years.

  12. Part 2: Duration of Response (DoR)

    Response defined as PMR (partial metabolic response) or better.

    Measured: From the date of first response until disease progression, assessed up to 4 years.

  13. Part 2: Duration of Complete Response (DoCR)

    Measured: From the date of first complete metabolic response (CMR) until disease progression, assessed up to 4 years.

  14. Part 2: Non-Relapse Mortality (NRM)

    NRM rates will be presented at 6 months and 1 year.

    Measured: NRM will be measured from the date of registration until the date of NRM. This will be assessed from the date of registration until up to 4 years. NRM rates will be presented at 6 months and 1 year.

  15. Part 2: Progression Free Survival (PFS) (at 12 months)

    Median (if reached), rate at 12 months (with 95% CI) and plot will be presented

    Measured: PSF will be measured from the date of registration at Part 2 until the date of disease progression. This will be assessed from the date of registration until up to 4 years. The median rate at 12 months will be presented.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2023
  2. Study start16 Aug 2024
  3. Primary completion30 Jul 2027 (estimated)
  4. Study completion30 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Part 1: 42 patients, Part 2: 42-57 patients (some Part 1 patients may also participate in Part 2)
Masking
None (open label)
Enrolment
99 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06071871
Sponsor's protocol ID
UCL/150862
Other IDs
2022-003727-17
Acronym
PORTAL
Status last verified
Dec 2024
First submitted
23 Aug 2023
Last updated
24 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kuhnl A, Kirkwood AA, Northend M, Alajangi R, Uttenthal B, Norman J, Hiew H, Seymour F, Maybury BD, Osborne W, Sillito F, Abdulgawad A, Jones C, Delaney A, Townsend W, Panopoulou A, Gribben JG, Bataillard E, Mathew A, Martinez-Calle N, Gajendran L, Davies AJ, Chavda N, Kumar E, Sanderson R, Kamat S, Petrides G, Roddie C, Menne T, Chaganti S. Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma. Blood Adv. 2026 Jun 9;10(11):3777-3786. doi: 10.1182/bloodadvances.2026019802.

    PubMed 41894687

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Glofitamab, Polatuzumab vedotin and Obinutuzumab in people with Large B-cell Lymphoma, run by University College, London at 5 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact PORTAL Trial Manager (020 7679 9860, ctc.portal@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Overall Response Rate (ORR) to Pola-Glofit as bridging prior to CAR-T cell infusion (time frame: At Cycle 2 Day 14-19 (or earlier) (each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06071871, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2024.

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