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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03467373




Registration number
NCT03467373
Ethics application status
Date submitted
9/03/2018
Date registered
9/03/2018
Date last updated
23/01/2019

Titles & IDs
Public title
A Study of RO7082859 in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Non-Hodgkin Lymphomas
Scientific title
A Phase 1B Study Evaluating RO7082859 in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) or in Participants With Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
Secondary ID [1] 0 0
2017-003648-18
Secondary ID [2] 0 0
NP40126
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-Cell Lymphoma 0 0
Non-Hodgkin 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 - RO7082859
Treatment: Drugs - Obinutuzumab (G)
Treatment: Drugs - Rituximab (R)
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone

Experimental: Part 1: Dose Escalation r/r NHL - Dose finding in participants with r/r NHL: the study will explore different doses of RO7082859 in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP on an every 3 weeks (Q3W) schedule. Participants with r/r NHL will receive 6 cycles (Cycles 1-6) of induction treatment (G/R-CHOP). RO7082859 will be administered in Cycles 2-6 on Day 8. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with RO7082859 alone.

Experimental: Part 2: Dose Expansion r/r NHL - Participants with r/r NHL will be assigned to an expansion cohort to further explore RO7082859 at the MTD/OBD determined in Part I.

Experimental: Part 2: DLBCL G-CHOP - Participants with untreated DLBCL will receive G-CHOP in Cycle 1, followed by R-CHOP + RO7082859 for 6-8 cycles. The starting dose of RO7082859 for each arm may be one or more levels below the MTD/OBD determined in Part I.

Experimental: Part 2: DLBCL R-CHOP - Participants with untreated DLBCL will receive R-CHOP in Cycle 1, followed by R-CHOP + RO7082859 for 6-8 cycles. The starting dose of RO7082859 for each arm may be one or more levels below the MTD/OBD determined in Part I.


Treatment: Drugs: RO7082859
RO7082859 will be administered intravenously (IV) at a dose and as per the schedule specified in the respective arms.

Treatment: Drugs: Obinutuzumab (G)
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

Treatment: Drugs: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 2 to Cycle 8 (Rituximab is administered from Cycles 1-8 for Part 2: DLBCL R-CHOP).

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Treatment: Drugs: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Treatment: Drugs: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

Treatment: Drugs: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 29 months
Primary outcome [2] 0 0
Part I and II: Percentage of Participants with Adverse Events
Timepoint [2] 0 0
Up to 29 months
Secondary outcome [1] 0 0
Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria
Timepoint [1] 0 0
Up to 29 months
Secondary outcome [2] 0 0
Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR])
Timepoint [2] 0 0
Up to 29 months
Secondary outcome [3] 0 0
Parts I and II: Duration of Response (DOR)
Timepoint [3] 0 0
Up to 29 months
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
Up to 29 months
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Up to 29 months
Secondary outcome [6] 0 0
Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of RO7082859
Timepoint [6] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [7] 0 0
Parts I and II: Time to Maximum Serum Concentration (tmax) of RO7082859
Timepoint [7] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [8] 0 0
Parts I and II: Maximum Serum Concentration (Cmax) of RO7082859
Timepoint [8] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [9] 0 0
Parts I and II: Minimum Serum Concentration (Cmin) of RO7082859
Timepoint [9] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [10] 0 0
Change from Baseline in T-cell Activation Markers
Timepoint [10] 0 0
Up to 29 months

Eligibility
Key inclusion criteria
- Age>/=18 years for participants with r/r NHL or > 60 years for participants with
untreated DLBCL

- For Part I r/r NHL dose-escalation, and Part II r/r NHL expansion:
Histologically-confirmed NHL that is expected to express CD20, and which has
relapsed/progressed following at least one prior treatment regimen containing R or G.
Participants must be appropriate for treatment with CHOP and typically should not have
been exposed to prior anthracyclines or must not exceed the cumulative lifetime dose
of anthracyclines

- For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated
DLBCL that is expected to express CD20

- Able to provide a pretreatment biopsy between the last dose of last prior therapy and
initiation of study medication at Cycle 1/Day 1

- Participants must have at least one measurable target lesion (> or = 1.5 cm) in its
largest dimension by computed tomography (CT) scan

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for
participants with r/r NHL; ECOG performance status 0-3 for participants with untreated
DLBCL

- Life expectancy (in the opinion of the Investigator) of 18 weeks

- Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade < or =
1

- Adequate liver function

- Adequate hematological function

- Adequate renal function

- Negative serologic or polymerase chain reaction (PCR) test results for acute or
chronic hepatitis B virus (HBV) infection

- Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus
(HIV)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inability to comply with protocol mandated hospitalization and restrictions

- Participants with known active infection, or reactivation of a latent infection,
whether bacterial, viral (including, but not limited to Epstein Barr virus (EBV), HBV,
HCV, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections
of nail beds) or any major episode of infection requiring hospitalization or treatment
with IV antibiotics (for IV antibiotics, this pertains to completion of last course of
antibiotic treatment) within 4 weeks of dosing

- Prior treatment with systemic immunotherapeutic agents, including, but not limited to,
radioimmuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal
antibodies (e.g., anti-CTLA4, anti-PD1, and anti-PDL1) within 4 weeks or five
half-lives of the drug, whichever is shorter, before G- or R-CHOP infusion on Cycle
1/Day 1

- History of treatment-emergent immune-related AEs associated with prior
immunotherapeutic agents, as follows: Grade >/=3 AEs, with the exception of Grade 3
endocrinopathy managed with replacement therapy; Grade 1-2 AEs that did not resolve to
baseline after treatment completion

- Contraindication to any of the individual components of the chemotherapy

- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with
any other investigational anti-cancer agent within 4 weeks prior to study treatment at
Cycle 1/Day 1 infusion

- Prior solid organ transplantation

- Prior allogeneic stem cell transplantation

- Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1

- History of autoimmune disease

- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibody therapy (or recombinant antibody-related fusion proteins)

- A history of confirmed progressive multifocal leukoencephalopathy

- Current or past history of central nervous system (CNS) lymphoma

- Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who
received corticosteroid treatment with </=30 mg/day of prednisone or equivalent must
be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle
1/Day 1. Participants may have received a brief (<7 days) course of systemic steroids
(</=100 mg prednisone equivalent per day) prior to initiation of study therapy for
control of lymphoma-related symptoms

- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or
neurodegenerative disease

- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including diabetes
mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary
disease), and known autoimmune diseases

- Major surgery or significant traumatic injury < 28 days prior to the study treatment
infusion at Cycle 1/Day 1 (excluding biopsies) or anticipation of the need for major
surgery during study treatment

- Participants with another invasive malignancy that could affect compliance with the
protocol or interpretation of results

- Significant cardiovascular disease

- Left ventricular ejection fraction < 50%

- Administration of a live, attenuated vaccine within 4 weeks before study treatment
infusion on Cycle 1 Day 1 or anticipation that such a live, attenuated vaccine will be
required during the study

- History of illicit drug or alcohol abuse within 12 months prior to screening, in the
Investigator's judgment

- Any other diseases, metabolic dysfunction, physical examination finding (including
mental status), or clinical laboratory finding giving reasonable suspicion of a
disease or condition that would contraindicate the use of an investigational drug

- Participants with latent or active tuberculosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
West Virginia
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Denmark
State/province [9] 0 0
København Ø
Country [10] 0 0
Germany
State/province [10] 0 0
Erlangen
Country [11] 0 0
Germany
State/province [11] 0 0
Freiburg
Country [12] 0 0
Germany
State/province [12] 0 0
Ulm
Country [13] 0 0
Germany
State/province [13] 0 0
Würzburg
Country [14] 0 0
Italy
State/province [14] 0 0
Emilia-Romagna
Country [15] 0 0
Italy
State/province [15] 0 0
Lombardia
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Leicester
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Plymouth

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 1B, multi-center, dose-finding study of RO7082859 administered in combination
with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or
R-CHOP) in participants with r/r NHL and untreated diffuse large B-cell lymphoma (DLBCL).
Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic
effects of this combination will be the main objectives of this study. The study is divided
in two parts:

- Part I: Dose finding in participants with r/r NHL

- Part II: Dose expansion in which the maximum tolerated dose (MTD) (or optimal biologic
dose [OBD]) determined in Part I will be further assessed in participants with r/r NHL
and those with untreated DLBCL (>60 years old with an age-adjusted International
Prognostic Index [IPI]) of 2-3), and the impact of using G in place of R in Cycle 1 on
safety and tolerability will be assessed via a randomized, unblinded, two-arm design in
participants with untreated DLBCL.
Trial website
https://clinicaltrials.gov/show/NCT03467373
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
Reference Study ID: NP40126 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable