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Relapsed Diffuse Large B-cell LymphomaPhase 3Pola-R-ICENCT04833114

Polatuzumab Vedotin Plus Rituximab, Ifosfamide, Carboplatin and Etoposide (Pola-R-ICE) Versus R-ICE Alone in Second Line Treatment of Diffuse Large B-cell Lymphoma (DLBCL)

A Phase 3 study testing Polatuzumab Vedotin, Mabthera and Ifosfamide in people with Relapsed Diffuse Large B-cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by GWT-TUD GmbH at 64 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

An open-label, prospective Phase III clinical study to compare polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed diffuse large B-cell lymphoma… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Polatuzumab Vedotin, Mabthera and Ifosfamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
306 participants
Where
64 sitesin 4 countries
Study dates
30 Apr 2021to 19 Dec 2025
Phase
Phase 3
Are there results?
None posted in the registry

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

  • The informed consent form must be signed before any study specific tests or procedures are done
  • Adult male and female patients ≥18 years (≥16 years in the UK*) at the time of inclusion in the study (* In the UK an "adult" means a person who has attained the age of 16 years, according to The Medicines for Human Use (Clinical Trials) Regulations 2004, Part 1 Point 2.)
  • Ability to understand and follow study-related instructions
  • Risk group: All patients with one of the following histologically defined entities: Histological diagnosis of primary refractory or relapsed aggressive B-cell non-Hodgkin lymphoma (B-NHL), confirmed by a biopsy of involved nodal or extranodal site. Patients with any of the following histologies can be included:
  • DLBCL not otherwise specified (NOS)
  • T-cell/histiocyte-rich large B-cell lymphoma
Show all 26Show fewer
  • Primary cutaneous DLBCL, leg type
  • Epstein-Barr virus (EBV)-positive DLBCL, NOS
  • DLBCL associated with chronic inflammation
  • Primary mediastinal (thymic) large B-cell lymphoma
  • High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
  • High-grade B-cell lymphoma, NOS
  • Refractory disease is defined as no complete remission to first line therapy; subjects who are intolerant to first line therapy are excluded. Three groups of patients are eligible:
  • Progressive disease (PD) as best response to first line therapy (biopsy not mandatory if diagnostic sample available).
  • Stable disease (SD) as best response after at least 4 cycles of first line therapy (e.g., 4 cycles of R-CHOP) (biopsy not mandatory if diagnostic sample available).
  • Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease or disease Progression after the partial response.
  • Relapsed disease is defined as complete remission to first line therapy followed by biopsy proven disease relapse.
  • Performance Status ECOG 0-2 at time of randomization or ECOG 3 at screening if this is DLBCL-related and has improved to ECOG 2 or less with a 7-day steroid treatment during the screening Phase (e.g. 1 mg/kg prednisone).
  • Information on all 5 International Prognostic Index (IPI) factors
  • Staging (PET-CT based-staging according to Lugano criteria 2014). Patients must have PET-positive lesions.
  • Subjects must have received adequate first line therapy including at a minimum: i) anti-CD20 monoclonal antibody unless Investigator determines that tumor is CD20 negative, and ii) an anthracycline containing chemotherapy Regimen
  • Intent to proceed to high-dose therapy (HDT) and stem cell transplantation (SCT) if response to second line therapy
  • Adequate hematological function, as defined by: hemoglobin ≥ 8 g/dL, absolute neutrophil count (ANC) ≥ 1.0 x 109/L OR ≥ 0.5 x 109/L if neutropenia is attributable to underlying disease and before the administration of steroids, and platelet count ≥ 75 x 109/L OR ≥ 50 x 109/L if thrombocytopenia is attributable to Underlying disease
  • Women of childbearing potential must have a negative pregnancy test result within 7 days prior to the first study drug Administration
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Who cannot join

  • Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months. In particular, patients with the following organ dysfunction caused by accompanying disorders are to be excluded:
  • Heart failure with left ventricular ejection fraction (LVEF) < 45%
  • Impaired pulmonary function with vital capacity (VC) or forced expiratory volume (FEV1) < 50% of normal (only in case of history of significant pulmonary disease)
  • Impaired renal function with glomerular filtration rate (GFR) < 50 mL/min (calculated)
  • Impaired liver function with alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or Bilirubin > 1.5 x upper limit of normal (ULN). If elevation is caused by the disease, threshold of 2.5 x ULN is accepted
  • Peripheral neuropathy > Grade II (2) Human immunodeficiency virus (HIV)-positivity with detectable viral load and/or a CD4+ count below 0.3/nL
Show all 26Show fewer
  • Hepatitis B and C as defined by seropositivity (HBsAG and anti HBe/ anti HBc; anti-Hc); in case of false positive serology (transfused antibodies) negative PCR-results will allow patient inclusion. Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and monthly for at least 12 months after the last cycle of study Treatment
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study inclusion or any unresolved major episode of infection (as evaluated by the investigator) within 1 week prior to Cycle 1 Day 1
  • Patients with suspected or latent tuberculosis. Latent tuberculosis needs to be confirmed by positive interferon-gamma release Assay
  • Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment
  • Richter's transformation or prior chronic lymphocytic leukemia (CLL)
  • Vaccination with a live vaccine within 4 weeks prior to Treatment
  • Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
  • Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
  • Received more than one line of therapy for DLBCL
  • Received polatuzumab vedotin as part of the first line therapy
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Ongoing treatment or study procedures within any other Investigational Medicinal Product (IMP) clinical trial with the exception of follow-up. In case of a preceding clinical trial, last application of the respective IMP(s) must have been done more than five elimination half-lives before start of study medication in this trial.
  • History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
  • History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure
  • Contraindications according to the Investigator´s Brochure (IB) of polatuzumab vedotin or the local Summary of Product Characteristics (SmPCs) of the used rituximab, ifosfamide, carboplatin or etoposide products
  • Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject's Safety
  • Pregnancy or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
  • Close affiliation with the investigator (e.g. a close relative) or persons working at the study site
  • Subject is an employee of the sponsor or involved Contract Research Organization
  • At study inclusion, any organ impairment due to lymphoma infiltration is NOT regarded as an exclusion criterion.

Trial locations and contacts

64 sites in 4 countries.

64 sites in 4 countries

Germany26 sites

  • Universitätsklinikum RWTH-Aachen

    Aachen

  • HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation

    Berlin, 13125

  • Städtisches Klinikum Braunschweig

    Braunschweig

  • DIAKO Ev.Diakonie-Krankenhaus gemeinnützige GmbH

    Bremen

  • Klinikum Chemnitz gGmbH

    Chemnitz

  • St. Johannes Hospital Dortmund

    Dortmund

  • Universitätsklinikum Dresden

    Dresden

  • Helios St. Johannes Klinik

    Duisburg

  • Klinik für Onkologie, Hämatologie und Palliativmedizin

    Düsseldorf, 40479

  • Universitätsklinikum Frankfurt

    Frankfurt

  • Georg-August-Universität Göttingen Universitätsmedizin Göttingen

    Göttingen

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

  • Universitätsklinikum Jena

    Jena

  • Westpfalz-Klinikum GmbH

    Kaiserslautern

  • Städtisches Krankenhaus Kiel

    Kiel

  • Klinikum Ludwigshafen

    Ludwigshafen

  • Universitätsklinikum Magdeburg

    Magdeburg

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz

  • Philipps-Universität Marburg

    Marburg

  • Universitätsklinikum Münster

    Münster

  • Klinikum Oldenburg

    Oldenburg

  • Unversitätsmedizin Rostock

    Rostock

  • Klinikum Stuttgart

    Stuttgart

  • Klinikum Mutterhaus

    Trier

  • Universitätsklinikum Ulm

    Ulm

  • Helios Universitätsklinikum Wuppertal

    Wuppertal

Other trials in Germany

Spain21 sites

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Hospital Germans Trias I Pujol

    Badalona, 08916

  • Hospital Clinic i Provincial de Barcelona

    Barcelona, 08036

  • Hospital Universitari Vall d'Hebron

    Barcelona, 8035

  • Hospital Universitario de Donostia

    Donostia / San Sebastian, 20014

  • Hospital Universitario de Cabueñes

    Gijón, 33394

  • Institut Català d'oncologia de L'Hospitalet (ICO-L'Hospitalet)

    L'Hospitalet de Llobregat, 08908

  • Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria, 35012

  • Clínica Universidad de Navarra (Madrid location)

    Madrid, 28027

  • Hospital Universitario Fundación Jimenez Díaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Universitario Virgen de la Arrixaca

    Murcia, 30003

  • Hospital Universitario Son Espases

    Palma, Balearic Islands, 07120

  • Clínica Universidad de Navarra (Pamplona location)

    Pamplona, 31008

  • Complejo Asistencial Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39908

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Complejo Hospitalario Universitario de Vigo

    Vigo, 36212

Other trials in Spain

United Kingdom9 sites

  • Belfast City Hospital

    Belfast, BT9 7AB

  • Royal Cornwall Hospital

    Cornwell, TR1 3LJ

  • St James University Hospital

    Leeds, LS9 7TF

  • University London College Hospitals

    London, NW1 2PG

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Nottingham City Hospital

    Nottingham, NG5 1PB

  • Derriford Hospital, Plymouth

    Plymouth, PL6 8DH

  • Queens Hospital, Romford

    Romford, RM7 0AG

  • University Hospital Southampton NHS

    Southampton, S016 6YD

Other trials in United Kingdom

Austria8 sites

  • UK Graz Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie

    Graz, 8036

  • LKH Hochsteiermark Standort Leoben Abteilung für Innere Medizin Department für Hämato-Onkologie

    Leoben, 8700

  • Ordensklinikum Linz GmbH- Elisabethinen: I. Interne Abteilung Hämato-Onkologie

    Linz, 4020

  • Kepler Universitätsklinikum Med Campus III, Univ.-Klinik für Hämatologie und Internistische Onkologie

    Linz, 4021

  • Landeskrankenhaus Salzburg

    Salzburg, 5020

  • AKH Meduni Wien Universitätsklinik für Innere Medizin I:

    Vienna, 1090

  • Hanusch Krankenhaus

    Vienna, 1140

  • Klinikum Wels-Grieskirchen Abteilung für Innere Medizin IV

    Wels, 4600

Other trials in Austria

About this study

Official title: Open-label, Prospective Phase III Clinical Study to Compare Polatuzumab Vedotin Plus Rituximab, Ifosfamide, Carboplatin and Etoposide (Pola-R-ICE) With Rituximab, Ifosfamide, Carboplatin and Etoposide (R-ICE) Alone as Salvage Therapy in Patients With Primary Refractory or Relapsed Diffuse Large B-cell Lymphoma (DLBCL)

An open-label, prospective Phase III clinical study to compare polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed diffuse large B-cell lymphoma (DLBCL)

Read the detailed description

The study is designed as an international, multicenter, open-label, two-arm, prospective phase III study to compare the treatment of polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with the combination of rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed DLBCL.

The study will involve study sites in Germany, UK, Spain, and Austria. It is planned to include 324 patients who will be randomized 1:1 to receive either treatment in the experimental arm (Pola-R-ICE) or in the standard arm (R-ICE) to end up with 308 evaluable subjects for the randomized part of the trial. Further 10 patients will be treated with Pola-R-ICE during the safety run-in phase.

The study consists of a screening/inclusion visit, three chemotherapy cycles, an end-of - treatment visit (EoT), and follow-up visits. For each subject, the total duration of the study will be approximately 3 months of treatment plus at least 21 months follow-up. The study will end when the last included patient will have passed the last follow-up visit (LPLFU). For the study as a whole, the primary outcome will be evaluated when the last included patient will have completed the 21 months follow-up period or has left the study prematurely.

For the study as a whole, the primary outcome will be evaluated when the last included patient will have completed the 21 months follow-up period or has left the study prematurely.

Being tested
Polatuzumab Vedotin, Mabthera, Ifosfamide, Carboplatin, Etoposide
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.

  • Polatuzumab VedotinDrug

    Polatuzumab vedotin 1.8 mg/kg will be administered intravenously on Day 1 of each 21-day cycle for up to 3 cycles.

  • MabtheraDrug

    Rituximab (Mabthera/Rituxan®) will be administered as per local practice at a dose of 375 mg/m2 intravenously on Day 1 of each 21-day cycle for up to 3 cycles.

  • IfosfamideDrug

    Ifosfamide 5000 mg/m² will be administered i.v. over a 24 hr period starting on cycle Day 2.

  • CarboplatinDrug

    Carboplatin AUC 5 max 800 mg will be administered i.v. on cycle Day 2.

  • EtoposideDrug

    Etoposide 100 mg/m² will be administered i.v. on cycle Days 1, 2 and 3.

Study groups in NCT04833114
Study groupRoleWhat they receive
Experimental Arm: Pola-R-ICEExperimentalcombination of standard chemotherapy with polatuzumab vedotin (Pola-R-ICE) Application
Receives: Drug: Polatuzumab Vedotin; Drug: Mabthera; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide
Standard Arm: R-ICEActive comparatorconventional treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE)
Receives: Drug: Mabthera; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

What is being measured

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

  1. Assessment of the event-free survival of patients with DLBCL at first progression and the occurrence of any of the following events:

    • Failure to achieve sufficient response in PET-CT (Deauville score 3 or less) at end of study treatment (metabolic CR)
    • Disease progression (PD)
    • Start of additional unplanned anti-tumor treatment (radiation therapy allowed)
    • Relapse after achieving CR
    • Death due to any cause

    Measured: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)

Secondary outcomes (19)

  1. Assessment of the rate of metabolic complete response.

    Number of complete remissions.

    Measured: Day of randomization until end weeks 12 treatment.

  2. Evaluation of the partial response rate.

    Number of partial responses.

    Measured: Day of randomization until end of 12 weeks treatment.

  3. Assessment of the overall response rate.

    Number of complete and partial responses.

    Measured: Day of randomization until end of 12 weeks treatment.

  4. Assessment duration of response.

    Time from documentation of tumor response to disease progression or relapse.

    Measured: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)

  5. Assessment of the rate of progressive disease.

    Number of progressive diseases.

    Measured: Day of randomization until end of 12 weeks treatment.

  6. Assessment of disease relapse.

    Number of relapses.

    Measured: Day of randomization until end of 12 weeks treatment.

  7. Assessment of progression free survival.

    Occurence of disease progression, relapse or death due to any cause.

    Measured: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)

  8. Assessment of overall survival.

    Measured: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)

  9. Assessment of the rate of patients proceeding to transplantation.

    Measured: Day of randomization until week 12.

  10. Assessment of the rate of patients with non-relapse mortality.

    Measured: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)

  11. Evaluation of the frequency of adverse and serious adverse events including the incidence and duration of the adverse events neutropenia and thrombocytopenia with grade 4.

    Measured: Day of Randomization until 28 days after start of last cycle or start of further therapy

  12. Assessment of the number of patients with treatment-related death.

    Measured: Day of Randomization until up week 12 or 2 months after week 12 but before start of further therapy

  13. To determine the number of patients with occurence of second malignancies

    Measured: Day of Randomization until Day of randomization until end of follow up (at least 21 months follow up)

  14. Assessment of the protocol adherence by the rate and duration of chemotherapy cycles patients received.

    Measured: Day of Randomizaton until week 12.

  15. Assessment of the cumulative and relative dose of each IMP( ifosfamide, carboplatin and etoposide, rituximab and of the polatuzumab vedotin) by quantitative measurement.

    Measured: Day of Randomizaton until week 12.

  16. Assessment of the change in health related quality of life by generic questionnaire.

    Scale scores to be obtained for the multi-items scales. Range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: Day of Randomization until weeks 12 and months 3 and 12 in follow up.

  17. Assessment of the change in health related quality of life by five-item questionnaire.

    Measured: Day of Randomization until weeks 12 and months 3 and 12 in follow up

  18. Assessment visual analogue scale to measure health state.

    This scale is provided with numbers from 0 to 100.100 is the best health state and 0 (zero) is the worst health state.

    Measured: Day of Randomization until weeks 12 and months 3 and 12 in follow up

  19. Functional assessment of the cancer therapy-lymphoma by general questions and specific questions for lymphoma.

    Assessment how lymphoma-specific symptoms impact quality of life.

    Measured: Day of Randomization until weeks 12 and months 3 and 12 in follow up.

Timeline

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

  1. First posted6 Apr 2021
  2. Study start30 Apr 2021
  3. Primary completion19 Dec 2025
  4. Study completion19 Dec 2025

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
306 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04833114
Sponsor's protocol ID
Pola-R-ICE
Other IDs
MO40599 / GLA 2017-R2
Acronym
Pola-R-ICE
Status last verified
Jun 2026
First submitted
10 Feb 2021
Last updated
10 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Polatuzumab Vedotin, Mabthera and Ifosfamide in people with Relapsed Diffuse Large B-cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by GWT-TUD GmbH at 64 sites in 4 countries.

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 26 inclusion and 26 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: finished, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in Germany, Spain, United Kingdom, Austria. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Assessment of the event-free survival of patients with DLBCL at first progression and the occurrence of any of the following events: (time frame: Day of randomization until end of follow up (12 weeks treatment and at least 21 months follow up)). 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 NCT04833114.

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 10 Jun 2026.

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