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

NCT ID: NCT04182204

Last Updated: 2025-12-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-07

Study Completion Date

2024-11-29

Brief Summary

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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).

Detailed Description

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The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.

Conditions

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Diffuse Large B-Cell Lymphoma

Keywords

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Lymphoma Large B-Cell Diffuse

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pola-R-GemOx (Stage 1)

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.

Group Type EXPERIMENTAL

Polatuzumab Vedotin

Intervention Type 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.

Rituximab

Intervention Type DRUG

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

Gemcitabine

Intervention Type DRUG

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

Oxaliplatin

Intervention Type DRUG

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

Pola-R-GemOx (Stage 2)

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.

Group Type EXPERIMENTAL

Polatuzumab Vedotin

Intervention Type 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.

Rituximab

Intervention Type DRUG

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

Gemcitabine

Intervention Type DRUG

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

Oxaliplatin

Intervention Type DRUG

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

R-GemOx (Stage 2)

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.

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

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

Gemcitabine

Intervention Type DRUG

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

Oxaliplatin

Intervention Type DRUG

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

Interventions

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Polatuzumab Vedotin

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.

Intervention Type DRUG

Rituximab

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

Intervention Type DRUG

Gemcitabine

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

Intervention Type DRUG

Oxaliplatin

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

Intervention Type DRUG

Other Intervention Names

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Mabthera; Rituxan

Eligibility Criteria

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Inclusion Criteria

* 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,

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Cancer Specialists

Jacksonville, Florida, United States

Site Status

Memorial Cancer Institute at Memorial West

Pembroke Pines, Florida, United States

Site Status

IHA Hematology Oncology Consultants - Ann Arbor

Ann Arbor, Michigan, United States

Site Status

MSKCC at Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center at Bergen

Montvale, New Jersey, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, Brazil

Site Status

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, Brazil

Site Status

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, Brazil

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Niagara Health Systems - St. Catherines General Site

St. Catharines, Ontario, Canada

Site Status

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Site Status

Hu Nan Provincial Cancer Hospital

Changsha, , China

Site Status

West China Hospital - Sichuan University

Chengdu, , China

Site Status

Cancer Center, Sun Yat-sen University of Medical Sciences

Guangzhou, , China

Site Status

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, , China

Site Status

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, , China

Site Status

Institute of Hematology and Hospital of Blood Disease

Tianjin, , China

Site Status

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status

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

Xi'an, , China

Site Status

Oulu University Hospital

Oulu, , Finland

Site Status

Tampere University Hospital

Tampere, , Finland

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital De Haut Leveque

Pessac, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

ICANS

Strasbourg, , France

Site Status

Hopital Bretonneau

Tours, , France

Site Status

Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Laiko General Hospital

Athens, , Greece

Site Status

Attiko Hospital

Athens, , Greece

Site Status

Tata Memorial Hospital

Mumbai, Maharashtra, India

Site Status

All India Institute of Medical Sciences ,Institute Rotary Cancer Hospital

New Delhi, National Capital Territory of Delhi, India

Site Status

Tata Medical Center

Kolkata, West Bengal, India

Site Status

St James' Hospital

Dublin, , Ireland

Site Status

Uni Degli Studi Di Bari, Policlinico

Bari, Apulia, Italy

Site Status

Azienda Ospedaliero-Universitaria Policlinico di Modena Ematologia

Modena, Emilia-Romagna, Italy

Site Status

Az. Osp. Uni Ria Policlinico Tor Vergata

Rome, Lazio, Italy

Site Status

USL 4 di Prato - Nuovo Ospeale di Prato

Prato, Tuscany, Italy

Site Status

Hospital de Especialidades Centro Medico Nacional La Raza

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Instituto Nacional de Cancerologia

Distrito Federal, , Mexico

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

Gyeongsang National University Hospital

Gyeongsangnam-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, Spain

Site Status

Hospital Univ. 12 de Octubre

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Dr. Peset

Valencia, , Spain

Site Status

Sakarya Universitesi Egitim ve Arastirma Hastanesi

Adapazari/Sakarya, , Turkey (Türkiye)

Site Status

Abdurrahman Yurtarslan Onkoloji Training and Research Hospital

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz Uni School of Medicine

Antalya, , Turkey (Türkiye)

Site Status

Istanbul Uni Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Kocaeli Universitesi Tip Fakultesi

Kocaeli, , Turkey (Türkiye)

Site Status

Amerikan HAstanesi Onkoloji Birimi Te?vikiye

Ni?anta??, , Turkey (Türkiye)

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Countries

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Russia Sweden United States Brazil Canada China Finland France Germany Greece India Ireland Italy Mexico South Korea Spain Turkey (Türkiye) United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-003727-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO40598

Identifier Type: -

Identifier Source: org_study_id