Clinical trial NCT04182204: 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
Official title: A Phase III, Open-Label, Multicenter, Randomized, Study Evaluating the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab Plus Gemcitabine Plus Oxaliplatin (R-GEMOX) Versus R-GEMOX Alone in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Lymphoma
Large B-Cell
Diffuse
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-12-02
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Stage 1: Percentage of Participants with Adverse Events (AEs)
timeFrame: From baseline until 90 days after last dose (up to approximately 55 months)
measure: Stage 2: Overall Survival (OS)
timeFrame: From randomization in RCT up to approximately 34 months
Secondary outcomes:
measure: Stage 1: Percentage of Participants with Peripheral Neuropathy
timeFrame: From baseline up to approximately 71 months
measure: Stage 1: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions
timeFrame: From baseline up to approx. 55 months
measure: Stage 1: Polatuzumab Vedotin Dose Intensity
timeFrame: From baseline up to approx. 55 months
measure: Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline
timeFrame: Baseline (Day 1 of Stage 1)
measure: Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline
timeFrame: Baseline up until Month 2 of the Post-Treatment Follow-up period (up to approx. 55 months)
measure: Stage 1: Percentage of Participants with Complete Response (CR)
timeFrame: From baseline up to approximately 55 months
measure: Stage 1: Percentage of Participants with Objective Response (OR)
timeFrame: From baseline up to approximately 55 months
measure: Stage 1: Best Overall Response (BOR)
timeFrame: From baseline up to approximately 71 months
measure: Stage 1: Progression Free Survival (PFS)
timeFrame: From baseline up to approximately 71 months
measure: Stage 1: Overall Survival (OS)
timeFrame: From baseline up to approximately 71 months
measure: Stage 1: Event Free Survival (EFS)
timeFrame: From baseline up to approximately 71 months
measure: Stage 2: Percentage of Participants with Objective Response (OR)
timeFrame: From randomization in RCT until up to 34 months
measure: Stage 2: Percentage of Participants with Complete Response (CR)
timeFrame: From randomization in RCT until up to 34 months
measure: Stage 2: Best Overall Response (BOR)
timeFrame: From randomization in RCT until up to 49 months
measure: Stage 2: Progression Free Survival (PFS)
timeFrame: From randomization in RCT until up to 49 months
measure: Stage 2: Duration of Response (DOR)
timeFrame: From randomization in RCT until up to 49 months
measure: Stage 2: Event Free Survival (EFS)
timeFrame: From randomization in RCT until up to 49 months
measure: Stage 2: Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score
timeFrame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
measure: Stage 2: Time to Deterioration in Physical Functioning and Fatigue
timeFrame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
measure: Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score
timeFrame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
measure: Stage 2: Time to Progression in Lymphoma Symptoms According to FACT-Lym Subscale
timeFrame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
measure: Stage 2: Change from Baseline in Peripheral Neuropathy According to FACT/GOG-NTX-12 Subscale Score
timeFrame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
measure: Stage 2: Percentage of Participants with Adverse Events (AEs)
timeFrame: From randomization in RCT until up to 34 months
measure: Stage 2: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions
timeFrame: From baseline in RCT up to approx. 34 months
measure: Stage 2: Polatuzumab Vedotin Dose Intensity
timeFrame: From baseline in RCT up to approx. 34 months
measure: Stage 2: Percentage of Participants with Peripheral Neuropathy
timeFrame: From randomization in RCT until up to 49 months
measure: Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline
timeFrame: Baseline (Day 1 of Stage 2)
measure: Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline
timeFrame: Baseline (Day 1 of Stage 2) up until Month 2 of the Post-Treatment Follow-up period (up to approx. 34 months)
Other outcomes:
measure: Stage 1: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL)
timeFrame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)
measure: Stage 2: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL)
timeFrame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)
Locations:
city: Jacksonville
country: United States
facility: Cancer Specialists
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute at Memorial West
state: Florida
city: Ann Arbor
country: United States
facility: IHA Hematology Oncology Consultants - Ann Arbor
state: Michigan
city: Basking Ridge
country: United States
facility: MSKCC at Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering - Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Bergen
state: New Jersey
city: Commack
country: United States
facility: MSKCC @ Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Câncer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas - FMUSP
state: São Paulo
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health Systems - St. Catherines General Site
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre - Glen Site
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre hospitalier regional de Trois-Rivieres
state: Quebec
city: Changsha
country: China
facility: Hu Nan Provincial Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital - Sichuan University
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University of Medical Sciences
city: Nanchang
country: China
facility: The 1st Affiliated Hospital of Nanchang Unversity
city: Nanning
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Tianjin City
country: China
facility: Institute of Hematology and Hospital of Blood Disease
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Nimes
country: France
facility: CHU de Nîmes - Hôpital Carémeau
city: Pessac
country: France
facility: Hopital De Haut Leveque
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: ICANS
city: Tours
country: France
facility: Hopital Bretonneau
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Laiko General Hospital
city: Athens
country: Greece
facility: Attiko Hospital
city: New Delhi
country: India
facility: All India Institute of Medical Sciences ,Institute Rotary Cancer Hospital
state: Delhi
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Kolkata
country: India
facility: Tata Medical Center
state: WEST Bengal
city: Dublin
country: Ireland
facility: St James' Hospital
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena Ematologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Az. Osp. Uni Ria Policlinico Tor Vergata
state: Lazio
city: Bari
country: Italy
facility: Uni Degli Studi Di Bari, Policlinico
state: Puglia
city: Prato
country: Italy
facility: USL 4 di Prato - Nuovo Ospeale di Prato
state: Toscana
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Hospital de Especialidades Centro Medico Nacional La Raza
state: Mexico CITY (federal District)
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Adapazari/Sakarya
country: Turkey
facility: Sakarya Universitesi Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Abdurrahman Yurtarslan Onkoloji Training and Research Hospital
city: Antalya
country: Turkey
facility: Akdeniz Uni School of Medicine
city: Istanbul
country: Turkey
facility: Istanbul Uni Istanbul Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Ni?anta??
country: Turkey
facility: Amerikan HAstanesi Onkoloji Birimi Te?vikiye
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Kings College Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: