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Diffuse Large B Cell LymphomaPhase 2P+R-ICENCT05221645

Pembrolizumab in Combination With R-ICE Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma

A Phase 2 study testing Pembrolizumab, Rituximab and Ifosfamide in people with Diffuse Large B Cell Lymphoma, run by University of Southampton at 2 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is an open-label, multicentre, randomised phase II trial in relapsed or refractory diffuse large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B Cell Lymphoma
What is being tested?
Pembrolizumab, Rituximab and Ifosfamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
2 sitesUnited Kingdom
Study dates
27 Jun 2022to 31 Dec 2026
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 +ve diffuse large B-cell lymphoma, preferably with sufficient diagnostic material, obtained either at diagnosis or relapse (the latter is preferable) that is available to forward to the Haematological Malignancies Diagnostic Service (HMDS) for gene expression profiling and central pathology review
  • Refractory to, or relapsed following, first-line or second-line treatments with rituximab concurrently with anthracycline or anthracenedione-based chemotherapy or similar (etoposide allowed if comorbid).
  • Refractory disease must fulfil one of the following:
  • Continuing partial response (PR) from termination of first-line treatment. It is strongly recommended the lymphoma be reconfirmed by biopsy however, if these procedures are deemed to be inappropriate, the CI may determine eligibility following review of the imaging results and disease history.
  • Continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the lymphoma by biopsy (preferred) is recommended but not mandatory.
  • Progressive disease (PD). Biopsy or reconfirmation of the lymphoma is recommended but not mandatory.
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  • Potentially eligible for high-dose therapy and peripheral blood progenitor cell rescue in the event of response
  • Positive lesions shown on baseline PET-CT must be compatible with CT defined anatomical tumour sites.
  • At least 2 demarcated lesions/nodes with a long axis >1.5 cm and a short axis equal to 1.0cm or 1 clearly demarcated lesion/node with a long axis >2.0cm and short axis of 1.0cm
  • Previous therapy related toxicity should have resolved to a grade that the investigator deems appropriate to commence further treatment
  • ECOG Performance Status 0 - 1
  • Has provided written informed consent
  • Willing to use acceptable contraception (see Section 4.6)
  • Aged 18 or over

Who cannot join

  • Previous lymphoma cancer treatment beyond third line
  • Radiotherapy or cytotoxic drugs within two weeks of trial treatment
  • Major surgery within 4 weeks of trial registration. If a subject had major surgery, more than 4 weeks ago, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
  • Treatment with any unlicensed drug within 4 weeks of trial treatment
  • History of stroke or intracranial haemorrhage within 6 months prior to registration
  • Pre-existing peripheral neuropathy grade >2
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  • Clinically significant cardiac disease (inc. unstable angina, acute myocardial infarction, congestive heart failure, a current LVEF of <40%) within 6 months of registration
  • Any significant uncontrolled medical condition or known hypersensitivity to the study drugs
  • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
  • Other past or current malignancy within 2 years prior to registration unless in the opinion of the investigator it does not contraindicate participation in the study. Subjects who have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
  • Known CNS involvement
  • Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
  • Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible.
  • Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible.
  • Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • Screening laboratory values :
  • platelets <75x109/L (unless due to lymphoma involvement of the bone marrow)
  • neutrophils <1.0x109/L (unless due to lymphoma involvement of the bone marrow)
  • creatinine >2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance >50mL/min)
  • total bilirubin >1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert's disease)
  • ALT/AST >2.5 times upper normal limit (unless due to lymphoma)
  • alkaline phosphatase >2.5 times upper normal limit (unless due to lymphoma)
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone will be eligible as will be patients with controlled Type I diabetes mellitus on a stable dose of insulin).
  • Patients who have previously undergone allogeneic transplantation.
  • Live vaccination within 28 days of study treatment.
  • Pregnant or lactating females. Women of child-bearing potential should have negative pregnancy test.
  • History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Known hypersensitivity to CHO cell products or any component of the pembrolizumab formulation.
  • Previous treatment with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Corticosteroid use >10 mg/day of prednisolone or equivalent, for purposes other than for lymphoma symptom control.
  • Patients receiving corticosteroid treatment with <10 mg/day of prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisolone 100 mg or equivalent could be given for a maximum of 14 days as a pre-phase. A dose of up to 10mg or prednisolone or equivalent may be used during the screening phase to control symptoms.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites
  • The Beatson West of Scotland Cancer Centre

    Glasgow, Glasgow, G12 0YN

  • Oxford Cancer & Haematology Centre, The Churchill Hospital

    Headington, Oxford, OX3 7LE

Other trials in United Kingdom

About this study

This is an open-label, multicentre, randomised phase II trial in relapsed or refractory diffuse large B-cell lymphoma.

Read the detailed description

The study has two treatment arms to which participants will be randomised on a 3:1 basis to the experimental arm. The control arm (Arm A) will be R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan). The experimental arm (Arm B) will consist of P+R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan) and maintenance Pembrolizumab every 3 weeks for one year.

All patients will be randomised at study entry and will be stratified by relapse within 12 months or > 12 months of first line therapy.

Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • PembrolizumabDrug

    Also called KEYTRUDA

    Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1. Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment of patients across a number of indications because of its mechanism of action to bind the PD-1 receptor on the T cell.

  • RituximabDrug

    Also called MabThera

    Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. Anti-CD20 mAbs, like rituximab, are classified by their CD20-binding characteristics, ability to induce complement-dependent cytotoxicity (CDC), and immune effector cell effects.

  • IfosfamideDrug

    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.

  • CarboplatinDrug

    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.

  • EtoposideDrug

    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.

Study groups in NCT05221645
Study groupRoleWhat they receive
Control Arm AActive comparatorPatients will receive three cycles of R-ICE. Each cycle is 21 days +/- 3 days Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2 All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol.
Receives: Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide
Experimental Arm BExperimentalPembrolizumab 200mg Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2 Patients will receive up to 3 cycles of: P+R-ICE, where each cycle is 21 days long +/-_3 days. All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing P+R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol. These patients will then be offered maintenance pembrolizumab every 3 weeks for one year.
Receives: Drug: Pembrolizumab; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

What is being measured

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

  1. To establish the event-free survival at 1 year in patients treated with P+R-ICE

    Event free survival at 1 year (binary) - the proportion of patients alive and event free at 1 year. An event is defined as any of the following:

    • Progression / relapse of lymphoma
    • Stable disease at 3 cycles of therapy
    • Commencement of any unplanned non-protocol treatment for lymphoma
    • Death from any cause

    Measured: 12 months

Secondary outcomes (11)
  1. Event free survival (EFS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve

    Event free survival (EFS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve - defined as time from day of registration until relapse or progression, unplanned re-treatment of lymphoma, or death as a result of any cause, whichever occurs first. Patients who do not experience an EFS event will be censored at the date of their last clinical follow-up.

    Measured: 12 months to 24 months

  2. Progression-free survival (PFS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve

    Progression-free survival (PFS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve - defined as the time from the day of registration to the date of progression or death from any cause, whichever occurs first. Patients who do not experience progression, or death will be censored at the date of their last clinical follow up.

    Measured: 12 months to 24 months

  3. Overall Survival (OS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve

    Overall Survival (OS) (time to event outcome) - median and at 1 and 2 years from Kaplan-meier curve - defined as the time from the day of registration to the date of death from any cause. Patients who do not die will be censored at the date of their last follow up.

    Measured: 12 months to 24 months

  4. Number of patients achieving 2 x 106 CD34 positive cells per kg stem cells on harvest

    Number of patients achieving 2 x 106 CD34 positive cells per kg stem cells on harvest

    Measured: 12 months

  5. The number and proportion of patients achieving CR at the end of induction

    The number and proportion of patients achieving CR at the end of induction (assessed by PET-CT at the end of cycle 3) determined by the Lugano response criteria

    Measured: 12 months

  6. The number and proportion of patients achieving CR at the end of transplantation.

    The number and proportion of patients achieving CR at the end of transplantation (PET-CT at week 27) determined by the Lugano response criteria. The Lugano response criteria determines a patient's response to treatment using a 1-4 staging to describe the spread of disease. Stage 1 being minimum spread of disease to stage 4 which is classed as a wide spread into at least one organ outside the lymph system. Clinicians will determine the Lugano response stage via a PET-CT image.

    Measured: 12 months

  7. Number and proportion of patients achieving CR at any point during follow up.

    Number and proportion of patients achieving CR at any point during follow up determined by the Lugano response criteria. The Lugano response criteria determines a patient's response to treatment using a 1-4 staging to describe the spread of disease. Stage 1 being minimum spread of disease to stage 4 which is classed as a wide spread into at least one organ outside the lymph system. Clinicians will determine the Lugano response stage via a PET-CT image.

    Measured: 12 months

  8. Number and proportion of patients with an Objective response at end of cycle 3.

    Number and proportion of patients with an Objective response (partial or complete metabolic response (PR or CR)) at end of induction assessed by PET-CT at end of cycle 3 determined by the Lugano response criteria. The Lugano response criteria determines a patient's response to treatment using a 1-4 staging to describe the spread of disease. Stage 1 being minimum spread of disease to stage 4 which is classed as a widespread into at least one organ outside the lymph system. Clinicians will determine the Lugano response stage via a PET-CT image.

    Measured: 12 months

  9. Number and proportion of patients with an Objective response at the end of transplantation.

    Number and proportion of patients with an Objective response (partial or complete metabolic response (PR or CR)) assessed by PET-CT at the end of transplantation (week 27) as determined by the Lugano response criteria. The Lugano response criteria determines a patient's response to treatment using a 1-4 staging to describe the spread of disease. Stage 1 is the minimum spread of disease to stage 4 which is classed as a widespread into at least one organ outside the lymph system. Clinicians will determine the Lugano response stage via a PET-CT image.

    Measured: 12 months

  10. Number and proportion of patients achieving an Objective response at any time point.

    Number and proportion of patients achieving an Objective response (CR or PR) at any point during follow up determined by the Lugano response criteria. The Lugano response criteria determines a patient's response to treatment using a 1-4 staging to describe the spread of disease. Stage 1 being the minimum spread of disease to stage 4 which is classed as a widespread into at least one organ outside the lymph system. Clinicians will determine the Lugano response stage via a PET-CT image.

    Measured: 12 months

  11. Frequency, severity and causality of adverse and serious adverse events.

    Frequency, severity and causality of adverse and serious adverse events severity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

    Measured: 12 months

Timeline

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

  1. First posted3 Feb 2022
  2. Study start27 Jun 2022
  3. Primary completion30 May 2026 (estimated)
  4. Study completion31 Dec 2026 (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
Randomised
Intervention model
Parallel groups
Model description
The study has two treatment arms to which participants will be randomised on a 3:1 basis to the experimental arm. The control arm (Arm A) will be R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan). The experimental arm (Arm B) will consist of P+R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan) and maintenance Pembrolizumab every 3 weeks for one year. All patients will be randomised at study entry and will be stratified by relapse within 12 months or \> 12 months of first line therapy.
Masking
None (open label)
Enrolment
65 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05221645
Sponsor's protocol ID
RHMCAN1402
Acronym
P+R-ICE
Status last verified
Feb 2026
First submitted
14 Oct 2021
Last updated
15 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Rituximab and Ifosfamide in people with Diffuse Large B Cell Lymphoma, run by University of Southampton at 2 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 14 inclusion and 33 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: under way, not looking for participants, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To establish the event-free survival at 1 year in patients treated with P+R-ICE (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 15 May 2026.

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