A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL).

NCT04236141 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: YO41543
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 10

Brief Summary

A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Randomisation will be conducted with the aid of an interactive web-based response system (IxRS).

Conditions

Diffuse, Large B-Cell, Lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC)

  CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.

  Up to approximately 23 weeks

Secondary Outcomes (20)

• Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator

  Up to approximately to 23 weeks

• Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator

  Up to approximately 23 weeks

• Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC

  Up to approximately 23 weeks

• Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator

  Up to approximately 23 weeks

• Percentage of Participants With CR at EOT Based on CT as Assessed by IRC

  Up to approximately 23 weeks

Study Arms (2)

Polatuzumab Vedotin plus BR

EXPERIMENTAL

Drug: Polatuzumab Vedotin; Drug: Bendamustine; Drug: Rituximab

Placebo plus BR

ACTIVE COMPARATOR

Drug: Bendamustine; Drug: Rituximab; Drug: Placebo

Interventions

Polatuzumab Vedotin DRUG

Participants will receive a total of 6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.

Polatuzumab Vedotin plus BR

Bendamustine DRUG

Participants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.

Placebo plus BR; Polatuzumab Vedotin plus BR

Rituximab DRUG

Participants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle.

Placebo plus BR; Polatuzumab Vedotin plus BR

Placebo DRUG

Participants will receive a total of 6 cycles (a cycle being 21 days) of Placebo (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.

Placebo plus BR

Eligibility Criteria

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

You may qualify if:

• Able to comply with the study protocol and procedures, in the investigator's judgement.
• Transplant ineligible participants with R/R DLBCL.
• Confirmed DLBCL diagnosis.
• For participants who have received prior bendamustine, a response duration \> 1 year (for participants who have relapsed disease after a prior regimen).
• At least one bi-dimensionally measurable lesion, defined as \> 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI).
• Availability of archival or freshly collected tumor tissue before study enrolment.
• Life expectancy of at least 24 weeks.
• ECOG Performance Status of 0, 1 or 2.
• Adequate haematologic function.
• Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.
• Residence in the People's Republic of China.

You may not qualify if:

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.
• Contraindication to bendamustine or rituximab.
• History of sensitivity to mannitol (mannitol is an excipient in bendamustine).
• Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1, Day 1.
• 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.
• Ongoing corticosteroid use \> 30 mg/day prednisone or equivalent, for purposes other than lymphoma symptom control.
• Completion of autologous SCT within 100 days prior to Cycle 1, Day 1.
• Prior allogeneic Stem Cell Transplantation (SCT).
• Prior treatment with Chimeric Antigen Receptor (CAR) T-cell therapy.
• Eligibility for autologous SCT.
• Grade 3b Follicular Lymphoma (FL).
• History of transformation of indolent disease to DLBCL.
• Primary or secondary CNS lymphoma.
• Current Grade \> 1 peripheral neuropathy.
• History of other malignancy that could affect compliance with the protocol or interpretation of results.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

Beijing Cancer Hospital

Beijing, 100142, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510663, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

Nanjing, 210029, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, 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

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Bendamustine Hydrochloride; Rituximab

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 22, 2020
• Study Start: July 10, 2020
• Primary Completion: July 12, 2021
• Study Completion: February 7, 2022
• Last Updated: March 3, 2023
• Results First Posted: August 4, 2022

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (10)