Clinical trial NCT04236141: 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).
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diffuse, Large B-Cell, Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-01-22
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular or pulmonary disease.
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1.
* Participants with suspected or latent tuberculosis.
* Positive Chronic Hepatitis B (HBV) infection or Hepatitis C (HCV) infection.
* Known history of HIV infection.
* Known infection human T-cell leukemia virus 1 virus.
* Vaccination with a live vaccine within 28 days prior to treatment.
* Recent major surgery (within 6 weeks before the start of Cycle 1, Day 1) other than for diagnosis.
* Pregnant or breastfeeding or intending to become pregnant during the study or within 12 months after the final dose of study treatment.
* 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 renders the patient at high risk from treatment complications.

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 23 weeks
Secondary outcomes:
measure: Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator
timeFrame: Up to approximately to 23 weeks
measure: Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With CR at EOT Based on CT as Assessed by IRC
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC
timeFrame: Up to approximately 23 weeks
measure: Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator
timeFrame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
measure: Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC
timeFrame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
measure: Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator
timeFrame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
measure: DOR Based on PET-CT/CT Only as Assessed by IRC
timeFrame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
measure: Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator
timeFrame: Up to approximately 82 weeks
measure: PFS Based on PET-CT/CT Only as Assessed by IRC
timeFrame: Up to approximately 82 weeks
measure: Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator
timeFrame: Up to approximately 82 weeks
measure: Overall Survival (OS)
timeFrame: Up to approximately 82 weeks
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 82 weeks
measure: Serum Concentration of Total Antibody at Specified Timepoints
timeFrame: Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks
measure: Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints
timeFrame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
measure: Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints
timeFrame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
measure: Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin
timeFrame: Baseline up to approximately 39 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou City
country: China
facility: Sun Yet-sen University Cancer Center
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Wuhan City
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: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: