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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02611323




Registration number
NCT02611323
Ethics application status
Date submitted
19/11/2015
Date registered
20/11/2015
Date last updated
10/10/2023

Titles & IDs
Public title
A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)
Scientific title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Secondary ID [1] 0 0
2015-001998-40
Secondary ID [2] 0 0
GO29833
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Rituximab
Treatment: Drugs - Polatuzumab Vedotin
Treatment: Drugs - Venetoclax

Experimental: Dose-Escalation Cohort: FL - Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.

Experimental: Dose-Escalation Cohort: DLBCL - Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.

Experimental: Expansion Cohort: FL - Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.

Experimental: Expansion Cohort: DLBCL - Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.


Treatment: Drugs: Obinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 milligrams (mg) via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month (starting from Month 2) for up to 24 months, until disease progression or unacceptable toxicity.

Treatment: Drugs: Rituximab
Participants will receive a fixed dose of rituximab, 375 milligrams per square meter (mg/m^2) via IV infusion to be given on Day 1 of Cycles 1 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month (starting from Month 2) for up to 8 months, until disease progression or unacceptable toxicity.

Treatment: Drugs: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.

Treatment: Drugs: Venetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
Timepoint [1] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)
Primary outcome [2] 0 0
FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From study start to 24 months after last dose of study drug (approximately 56 months)
Primary outcome [3] 0 0
DLBCL Cohorts: Percentage of Participants With AEs and SAEs
Timepoint [3] 0 0
From study start to 3 months after last dose of study drug (approximately 21 months)
Primary outcome [4] 0 0
Number of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [4] 0 0
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Primary outcome [5] 0 0
RP2D of Polatuzumab Vedotin
Timepoint [5] 0 0
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Primary outcome [6] 0 0
RP2D of Venetoclax
Timepoint [6] 0 0
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Secondary outcome [1] 0 0
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
Timepoint [1] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [2] 0 0
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
Timepoint [2] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [3] 0 0
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
Timepoint [3] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [4] 0 0
Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans
Timepoint [4] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [5] 0 0
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans
Timepoint [5] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [6] 0 0
Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone
Timepoint [6] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [7] 0 0
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
Timepoint [7] 0 0
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Secondary outcome [8] 0 0
Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
Timepoint [8] 0 0
Up to every 6 months until disease progression, the start of new anti-lymphoma treatment, or the end of the study, whichever occurs first (approximately 77 months)
Secondary outcome [9] 0 0
Observed Serum Obinutuzumab Concentration
Timepoint [9] 0 0
Pre-dose & 0.5 hours post-dose on Day 1 Cycles 1, 2, 4, & 6; and pre-dose on Day 1 of Months 2, 8, 14, 20; study drug discontinuation, Day 120 &1 year post-last dose (up to approximately 40 months) (1 cycle = 21 days)
Secondary outcome [10] 0 0
Observed Serum Rituximab Concentration
Timepoint [10] 0 0
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1 and 6; pre-dose on Day 1 of Cycles 2 and 4; (1 cycle = 21 days)
Secondary outcome [11] 0 0
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
Timepoint [11] 0 0
Pre-dose on Day 1 of Cycles 1, 2 and 4; study drug discontinuation visit; Day 120 and 1 year post-last dose (up to approximately 16 months) (1 cycle=21 days)
Secondary outcome [12] 0 0
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
Timepoint [12] 0 0
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)
Secondary outcome [13] 0 0
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
Timepoint [13] 0 0
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)
Secondary outcome [14] 0 0
Observed Plasma Venetoclax Concentration
Timepoint [14] 0 0
Pre-dose and 4 hours post-dose on Day 1 Cycle 1, pre-dose & 2, 4, 6, & 8 hours post-dose on Day 1 Cycle 2, pre-dose & 4hours post-dose on Day 1 Cycle 4 & pre-dose on Day 1 Cycle 6; (1 cycle = 21 days)
Secondary outcome [15] 0 0
Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Timepoint [15] 0 0
Baseline up to approximately 2 years after last dose (up to approximately 56 months)
Secondary outcome [16] 0 0
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
Timepoint [16] 0 0
Baseline up to 1 year post last dose (up to approximately 16 months)

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or
refractory FL after treatment with at least one prior chemoimmunotherapy regimen that
included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody
(mAb) and for which no other more appropriate treatment option exists, as determined
by the investigator

- For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or
refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen
that included an anti-CD20 mAb and for which no curative option exists as determined
by the investigator

- At least one bidimensionally measurable lesion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known CD20-negative status at relapse or progression

- Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days
prior to Day 1 of Cycle 1

- Grade 3b FL

- History of transformation of indolent disease to DLBCL

- Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or
equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate within 12
weeks; mAb or antibody-drug conjugate within 4 weeks; or
radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2
weeks prior to Day 1 of Cycle 1

- Central nervous system (CNS) disease

- Active infection

- Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for
warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior
to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star
fruit within 3 days prior to first dose of venetoclax

- Positive for human immunodeficiency virus (HIV) or hepatitis B or C

- Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1

- Poor hematologic, renal, or hepatic function

- Pregnant or lactating women

- Life expectancy <3 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/08/2022
Sample size
Target
Accrual to date
Final
133
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital; Haematology Department - St. Leonards
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5011 - Adelaide
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Italy
State/province [11] 0 0
Emilia-Romagna
Country [12] 0 0
Italy
State/province [12] 0 0
Lombardia
Country [13] 0 0
Italy
State/province [13] 0 0
Piemonte

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment
with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or
refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with
DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or
stable disease (SD) at the end of induction therapy will receive post-induction treatment
with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end
of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02611323
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries