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)

NCT ID: NCT04833114

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2025-12-31

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)

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm: Pola-R-ICE

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

Group Type: EXPERIMENTAL

Polatuzumab Vedotin

Intervention Type: DRUG

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

Mabthera

Intervention Type: 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.

Ifosfamide

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Standard Arm: R-ICE

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

Group Type: ACTIVE_COMPARATOR

Mabthera

Intervention Type: 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.

Ifosfamide

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Interventions

Polatuzumab Vedotin

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

Intervention Type: DRUG

Mabthera

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.

Intervention Type: DRUG

Ifosfamide

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Etoposide

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

2. 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.)

3. Ability to understand and follow study-related instructions

4. 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.

Relapsed disease is defined as complete remission to first line therapy followed by biopsy proven disease relapse.

5. 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).

6. Information on all 5 International Prognostic Index (IPI) factors

7. Staging (PET-CT based-staging according to Lugano criteria 2014). Patients must have PET-positive lesions.

8. 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

9. Intent to proceed to high-dose therapy (HDT) and stem cell transplantation (SCT) if response to second line therapy

10. 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

11. Women of childbearing potential must have a negative pregnancy test result within 7 days prior to the first study drug Administration

12. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs

13. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

(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

(3) 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

(4) 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

(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

(14) 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.

(15) History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies

(16) History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure

(17) 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

(18) 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

(19) Pregnancy or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug

(20) Close affiliation with the investigator (e.g. a close relative) or persons working at the study site

(21) 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

GWT-TUD GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bertram Glaß, Prof.

Role: PRINCIPAL_INVESTIGATOR

HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation

Locations

UK Graz Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie

Graz, , Austria

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

Leoben, , Austria

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

Linz, , Austria

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

Linz, , Austria

Landeskrankenhaus Salzburg

Salzburg, , Austria

AKH Meduni Wien Universitätsklinik für Innere Medizin I:

Vienna, , Austria

Hanusch Krankenhaus

Vienna, , Austria

Klinikum Wels-Grieskirchen Abteilung für Innere Medizin IV

Wels, , Austria

Universitätsklinikum RWTH-Aachen

Aachen, , Germany

HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation

Berlin, , Germany

Städtisches Klinikum Braunschweig

Braunschweig, , Germany

DIAKO Ev.Diakonie-Krankenhaus gemeinnützige GmbH

Bremen, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

St. Johannes Hospital Dortmund

Dortmund, , Germany

Universitätsklinikum Dresden

Dresden, , Germany

Helios St. Johannes Klinik

Duisburg, , Germany

Klinik für Onkologie, Hämatologie und Palliativmedizin

Düsseldorf, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Georg-August-Universität Göttingen Universitätsmedizin Göttingen

Göttingen, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Städtisches Krankenhaus Kiel

Kiel, , Germany

Klinikum Ludwigshafen

Ludwigshafen, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Philipps-Universität Marburg

Marburg, , Germany

Universitätsklinikum Münster

Münster, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Unversitätsmedizin Rostock

Rostock, , Germany

Klinikum Stuttgart

Stuttgart, , Germany

Klinikum Mutterhaus

Trier, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Helios Universitätsklinikum Wuppertal

Wuppertal, , Germany

Hospital Universitario Son Espases

Palma, Balearic Islands, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Germans Trias I Pujol

Badalona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario de Donostia

Donostia / San Sebastian, , Spain

Hospital Universitario de Cabueñes

Gijón, , Spain

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

L'Hospitalet de Llobregat, , Spain

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, , Spain

Clínica Universidad de Navarra (Madrid location)

Madrid, , Spain

Hospital Universitario Fundación Jimenez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Clínica Universidad de Navarra (Pamplona location)

Pamplona, , Spain

Complejo Asistencial Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Complejo Hospitalario Universitario de Vigo

Vigo, , Spain

Belfast City Hospital

Belfast, , United Kingdom

Royal Cornwall Hospital

Cornwell, , United Kingdom

St James University Hospital

Leeds, , United Kingdom

University London College Hospitals

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Derriford Hospital, Plymouth

Plymouth, , United Kingdom

Queens Hospital, Romford

Romford, , United Kingdom

University Hospital Southampton NHS

Southampton, , United Kingdom

Countries

Austria; Germany; Spain; United Kingdom

Other Identifiers

MO40599 / GLA 2017-R2

Identifier Type: OTHER

Identifier Source: secondary_id

Pola-R-ICE

Identifier Type: -

Identifier Source: org_study_id