A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT04182204 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: MO405982018-003727-10
• Study Type: interventional
• Target: 270
• Locations: 16 countries
• Sites: 62

Brief Summary

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Lymphoma; Large B-Cell; Diffuse

Outcome Measures

Primary Outcomes (3)

• Stage 1: Number of Participants With Adverse Events (AEs)

  An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)

• Stage 1: Number of Participants With Peripheral Neuropathy (PN)

  An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.

  From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months)

• Stage 2: Overall Survival (OS)

  OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm.

  From randomization to death (Up to approximately 34 months)

Secondary Outcomes (24)

• Stage 1 and Stage 2: Progression-free Survival (PFS)

  From randomization to first occurrence of PD or death (Up to approximately 34 months)

• Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment

  Up to approximately 8.5 months

• Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment

  Up to approximately 8.5 months

• Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator

  Up to approximately 34 months

• Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment

  Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months

Study Arms (3)

Pola-R-GemOx (Stage 1)

EXPERIMENTAL

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m\^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

Pola-R-GemOx (Stage 2)

EXPERIMENTAL

Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

R-GemOx (Stage 2)

ACTIVE COMPARATOR

Participants will receive rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Polatuzumab Vedotin DRUG

Polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.

Pola-R-GemOx (Stage 1); Pola-R-GemOx (Stage 2)

Rituximab DRUG

Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.

Also known as: Mabthera; Rituxan

Pola-R-GemOx (Stage 1); Pola-R-GemOx (Stage 2); R-GemOx (Stage 2)

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.

Pola-R-GemOx (Stage 1); Pola-R-GemOx (Stage 2); R-GemOx (Stage 2)

Oxaliplatin DRUG

Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.

Pola-R-GemOx (Stage 1); Pola-R-GemOx (Stage 2); R-GemOx (Stage 2)

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL
• Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that did not respond to or that progressed during therapy or progressed within 6 months (\< 6 months) of prior therapy)
• At least one (≥ 1) line of prior systemic therapy:
• Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; In such cases, salvage chemotherapy (e.g., rituximab, dexamethasone, cytarabine, and cisplatin \[R-DHAP\] and rituximab, ifosfamide, carboplatin, and etoposide phosphate \[R-ICE\]) will be counted as one line of therapy and conditioning chemotherapy (e.g., BEAM) followed by consolidative autologous HSCT will be counted as one line of therapy
• Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; In such cases, salvage chemotherapy (e.g., R-DHAP and R-ICE) will be counted as one line of therapy and conditioning chemotherapy (e.g., carmustine, etoposide, cytarabine, and melphalan \[BEAM\]) followed by allogeneic HSCT will be counted as a separate line of therapy
• Participants may have undergone CAR T-cell therapy prior to recruitment. In such cases, cell collection, conditioning chemotherapy, and infusion will be counted as one line of therapy.
• Local therapies (e.g., radiotherapy) will not be considered as lines of treatment
• For participants with a history of the transformation of indolent disease to DLBCL, it is preferred that participants have received at least one treatment for the transformed lymphoma. However, if there are cases where the participants have received an anthracycline-containing chemotherapy regimen (such as R-CHOP) for the indolent lymphoma only, then these participants can be considered as eligible.
• At least one bi-dimensionally measurable lesion, defined as \> 1.5 cm in its longest dimension as measured by CT or MRI
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
• Adequate hematological function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, 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,

You may not qualify if:

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to rituximab, gemcitabine or oxaliplatin
• Peripheral neuropathy assessed to be \> Grade 1 according to NCI CTCAE v5.0
• Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks
• Planned autologous or allogenic stem cell transplantation or CAR T-cell therapy at time of recruitment
• Primary or secondary central nervous system (CNS) lymphoma
• Richter's transformation or prior CLL
• Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
• 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
• 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
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
• Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (62)

Cancer Specialists

Jacksonville, Florida, 32256, United States

Location

Memorial Cancer Institute at Memorial West

Pembroke Pines, Florida, 33028, United States

Location

IHA Hematology Oncology Consultants - Ann Arbor

Ann Arbor, Michigan, 48106, United States

Location

MSKCC at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center at Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, 59040150, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, DUMMY_VALUE, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Niagara Health Systems - St. Catherines General Site

St. Catharines, Ontario, L2R 7C6, Canada

Location

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Hu Nan Provincial Cancer Hospital

Changsha, 410006, China

Location

West China Hospital - Sichuan University

Chengdu, 610047, China

Location

Cancer Center, Sun Yat-sen University of Medical Sciences

Guangzhou, 510060, China

Location

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, 330006, China

Location

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, 530021, China

Location

Institute of Hematology and Hospital of Blood Disease

Tianjin, 300020, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

Oulu University Hospital

Oulu, 90029, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital De Haut Leveque

Pessac, 33604, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

ICANS

Strasbourg, 67200, France

Location

Hopital Bretonneau

Tours, 37044, France

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Laiko General Hospital

Athens, 115 27, Greece

Location

Attiko Hospital

Athens, 124 62, Greece

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400013, India

Location

All India Institute of Medical Sciences ,Institute Rotary Cancer Hospital

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Tata Medical Center

Kolkata, West Bengal, 700160, India

Location

St James' Hospital

Dublin, DUMMY_VALUE, Ireland

Location

Uni Degli Studi Di Bari, Policlinico

Bari, Apulia, 70124, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena Ematologia

Modena, Emilia-Romagna, 41123, Italy

Location

Az. Osp. Uni Ria Policlinico Tor Vergata

Rome, Lazio, 00133, Italy

Location

USL 4 di Prato - Nuovo Ospeale di Prato

Prato, Tuscany, 59100, Italy

Location

Hospital de Especialidades Centro Medico Nacional La Raza

Mexico City, Mexico CITY (federal District), 02990, Mexico

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Instituto Nacional de Cancerologia

Distrito Federal, 14080, Mexico

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Gyeongsang National University Hospital

Gyeongsangnam-do, 52727, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08915, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Hospital Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Sakarya Universitesi Egitim ve Arastirma Hastanesi

Adapazari/Sakarya, 54100, Turkey (Türkiye)

Location

Abdurrahman Yurtarslan Onkoloji Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

Location

Akdeniz Uni School of Medicine

Antalya, 07059, Turkey (Türkiye)

Location

Istanbul Uni Istanbul Medical Faculty

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Amerikan HAstanesi Onkoloji Birimi Te?vikiye

Ni?anta??, 34365, Turkey (Türkiye)

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

polatuzumab vedotin; Rituximab; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; 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; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: In stage 1 participants are all assigned to one group. In stage 2 participants are assigned to two groups in parallel for the duration of the study.

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: December 2, 2019
• Study Start: February 7, 2020
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: December 22, 2025
• Results First Posted: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7); GR (2); BR (4); IN (3); ME (3); FI (2); ES (5); FR (5); CN (8); GB (2); IE (1); KR (5); DE (1); CA (3); IT (4); TU (7)