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)

NCT04833114 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: Pola-R-ICEMO40599 / GLA 2017-R2
• Study Type: interventional
• Target: 306
• Locations: 4 countries
• Sites: 64

Brief 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 (DLBCL)

Conditions

Relapsed Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (19)

• Assessment of the rate of metabolic complete response.

  Day of randomization until end weeks 12 treatment.

• Evaluation of the partial response rate.

  Day of randomization until end of 12 weeks treatment.

• Assessment of the overall response rate.

  Day of randomization until end of 12 weeks treatment.

• Assessment duration of response.

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

• Assessment of the rate of progressive disease.

  Day of randomization until end of 12 weeks treatment.

Study Arms (2)

Experimental Arm: Pola-R-ICE

EXPERIMENTAL

combination of standard chemotherapy with polatuzumab vedotin (Pola-R-ICE) Application

Drug: Polatuzumab Vedotin; Drug: Mabthera; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

Standard Arm: R-ICE

ACTIVE COMPARATOR

conventional treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE)

Drug: Mabthera; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

Interventions

Polatuzumab Vedotin DRUG

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

Experimental Arm: Pola-R-ICE

Mabthera DRUG

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.

Experimental Arm: Pola-R-ICE; Standard Arm: R-ICE

Ifosfamide DRUG

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

Experimental Arm: Pola-R-ICE; Standard Arm: R-ICE

Carboplatin DRUG

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

Experimental Arm: Pola-R-ICE; Standard Arm: R-ICE

Etoposide DRUG

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

Experimental Arm: Pola-R-ICE; Standard Arm: R-ICE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The informed consent form must be signed before any study specific tests or procedures are done
• 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
• 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.

You may not qualify if:

• (1) 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
• (5) Patients with suspected or latent tuberculosis. Latent tuberculosis needs to be confirmed by positive interferon-gamma release Assay
• (6) Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment
• (7) Richter's transformation or prior chronic lymphocytic leukemia (CLL)
• (8) Vaccination with a live vaccine within 4 weeks prior to Treatment
• (9) Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
• (10) 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
• (11) Received more than one line of therapy for DLBCL
• (12) Received polatuzumab vedotin as part of the first line therapy
• (13) 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

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Hoffmann-La Roche: collaborator

Study Sites (64)

UK Graz Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie

Graz, 8036, Austria

Location

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

Leoben, 8700, Austria

Location

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

Linz, 4020, Austria

Location

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

Linz, 4021, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

AKH Meduni Wien Universitätsklinik für Innere Medizin I:

Vienna, 1090, Austria

Location

Hanusch Krankenhaus

Vienna, 1140, Austria

Location

Klinikum Wels-Grieskirchen Abteilung für Innere Medizin IV

Wels, 4600, Austria

Location

Universitätsklinikum RWTH-Aachen

Aachen, Germany

Location

HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation

Berlin, 13125, Germany

Location

Städtisches Klinikum Braunschweig

Braunschweig, Germany

Location

DIAKO Ev.Diakonie-Krankenhaus gemeinnützige GmbH

Bremen, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Germany

Location

St. Johannes Hospital Dortmund

Dortmund, Germany

Location

Universitätsklinikum Dresden

Dresden, Germany

Location

Helios St. Johannes Klinik

Duisburg, Germany

Location

Klinik für Onkologie, Hämatologie und Palliativmedizin

Düsseldorf, 40479, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Georg-August-Universität Göttingen Universitätsmedizin Göttingen

Göttingen, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, Germany

Location

Städtisches Krankenhaus Kiel

Kiel, Germany

Location

Klinikum Ludwigshafen

Ludwigshafen, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Germany

Location

Philipps-Universität Marburg

Marburg, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Klinikum Oldenburg

Oldenburg, Germany

Location

Unversitätsmedizin Rostock

Rostock, Germany

Location

Klinikum Stuttgart

Stuttgart, Germany

Location

Klinikum Mutterhaus

Trier, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Helios Universitätsklinikum Wuppertal

Wuppertal, Germany

Location

Hospital Universitario Son Espases

Palma, Balearic Islands, 07120, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario de Donostia

Donostia / San Sebastian, 20014, Spain

Location

Hospital Universitario de Cabueñes

Gijón, 33394, Spain

Location

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

L'Hospitalet de Llobregat, 08908, Spain

Location

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, 35012, Spain

Location

Clínica Universidad de Navarra (Madrid location)

Madrid, 28027, Spain

Location

Hospital Universitario Fundación Jimenez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30003, Spain

Location

Clínica Universidad de Navarra (Pamplona location)

Pamplona, 31008, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39908, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, 36212, Spain

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Royal Cornwall Hospital

Cornwell, TR1 3LJ, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

University London College Hospitals

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Derriford Hospital, Plymouth

Plymouth, PL6 8DH, United Kingdom

Location

Queens Hospital, Romford

Romford, RM7 0AG, United Kingdom

Location

University Hospital Southampton NHS

Southampton, S016 6YD, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Rituximab; Ifosfamide; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Bertram Glaß, Prof.

  HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: April 6, 2021
• Study Start: April 30, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

ES (21); AU (8); DE (26); GB (9)