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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02055820




Registration number
NCT02055820
Ethics application status
Date submitted
4/02/2014
Date registered
5/02/2014
Date last updated
11/06/2020

Titles & IDs
Public title
A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax Combined With Chemotherapy in Participants With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL
Scientific title
A Phase Ib/II, Open-Label Study Evaluating the Safety, Efficacy and Pharmacokinetics of GDC-0199 (ABT-199) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL
Secondary ID [1] 0 0
2013-003749-40
Secondary ID [2] 0 0
GO27878
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 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 - Venetoclax
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Rituximab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone

Experimental: Venetoclax + G-CHOP Arm - Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

Experimental: Venetoclax + R-CHOP Arm - Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.


Treatment: Drugs: Venetoclax
Venetoclax 200 to 800 milligrams (mg) tablets will be administered orally once daily (QD) on Days 4-10 of Cycle 1 and Days 1-10 of Cycles 2-8 during Phase I and MTD will be administered according to the same schedule during Phase II.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide 750 milligrams per square meter (mg/m\^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.

Treatment: Drugs: Obinutuzumab
Obinutuzumab will be administered by IV infusion as an absolute dose of 1000 mg on Days 1, 8, 15 of Cycle 1 and Day 1 of Cycles 2-8 (cycle length = 21 days).

Treatment: Drugs: Rituximab
Rituximab 375 mg/m\^2 dose will be administered IV on Day 1 of every 21-day cycle.

Treatment: Drugs: Doxorubicin
Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.

Treatment: Drugs: Vincristine
Vincristine 1.4 mg/m\^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.

Treatment: Drugs: Prednisone
Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.

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

Outcomes
Primary outcome [1] 0 0
Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Start of venetoclax administration (Cycle 1 Day 4 or 3 days after first CHOP dose) up to end of Cycle 2 (cycle length = 21 days)
Primary outcome [2] 0 0
Percentage of Previously Untreated DLBCL Participants With Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET/CT) Scan Using the Modified Lugano Classification Assessed by Independent Review Committee (IRC)
Timepoint [2] 0 0
Baseline up to end of treatment (up to approximately 6 months)
Primary outcome [3] 0 0
Percentage of Participants With CR Defined by PET/CT Scan in Previously Untreated DLBCL Co-Expressing Both Bcl-2 and c-Myc Proteins (DE-DLBCL) Participants Assessed by IRC
Timepoint [3] 0 0
Baseline up to end of treatment (up to approximately 6 months)
Secondary outcome [1] 0 0
Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)
Timepoint [1] 0 0
Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)
Secondary outcome [2] 0 0
Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)
Timepoint [2] 0 0
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
Secondary outcome [3] 0 0
Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)
Timepoint [3] 0 0
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
Secondary outcome [4] 0 0
Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) Within the Dosing Interval
Timepoint [4] 0 0
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
Secondary outcome [5] 0 0
Prednisone Plasma PK: AUC
Timepoint [5] 0 0
Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
Secondary outcome [6] 0 0
Prednisone Plasma PK: Tmax
Timepoint [6] 0 0
Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
Secondary outcome [7] 0 0
Prednisone Plasma PK: Cmax
Timepoint [7] 0 0
Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
Secondary outcome [8] 0 0
Rituximab PK: Cmax
Timepoint [8] 0 0
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
Secondary outcome [9] 0 0
Rituximab PK: Cmin Within the Dosing Interval
Timepoint [9] 0 0
Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)
Secondary outcome [10] 0 0
Obinutuzumab PK: Cmax
Timepoint [10] 0 0
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
Secondary outcome [11] 0 0
Cyclophosphamide PK: Cmax
Timepoint [11] 0 0
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
Secondary outcome [12] 0 0
Doxorubicin PK: Cmax
Timepoint [12] 0 0
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
Secondary outcome [13] 0 0
Vincristine PK: Cmax
Timepoint [13] 0 0
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
Secondary outcome [14] 0 0
Percentage of Participants With Objective Response Defined as Partial Response (PR) or Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET/CT) Using the Modified Lugano Classification Assessed by IRC
Timepoint [14] 0 0
Baseline to end of treatment (up to approximately 6 months)
Secondary outcome [15] 0 0
Percentage of Participants Who Are Alive and Without Disease Progression at Month 12
Timepoint [15] 0 0
Month 12
Secondary outcome [16] 0 0
Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification
Timepoint [16] 0 0
Baseline up to end of treatment (approx. 6 months)
Secondary outcome [17] 0 0
Safety: Percentage of Participants With Adverse Events
Timepoint [17] 0 0
Baseline up to approximately 36 months
Secondary outcome [18] 0 0
Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy
Timepoint [18] 0 0
Baseline up to Cycle 6 (cycle length = 21 days)
Secondary outcome [19] 0 0
Relative Dose Intensity of Venetoclax
Timepoint [19] 0 0
Baseline up to Cycle 6 (cycle length = 21 days)

Eligibility
Key inclusion criteria
General

* At least one bi-dimensionally measurable lymphoma lesion on CT scan defined as > 1.5 cm in its longest dimension, which is also FDG avid by screening PET scan.
* Confirmed availability of archival or freshly biopsied tumor tissue prior to study enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Adequate hematologic function
* For female participants of childbearing potential, agreement to use highly effective forms of contraception

Dose-Escalation Portion of the Study:

* Participants must have histologically confirmed B-cell NHL, except MCL or SLL
* Participants must have never received previous R-CHOP treatment
* Any relapsed/refractory participants that are enrolled during the dose escalation should have received only a single previous treatment regimen

Expansion Portion of the Study:

* Participants must have previously untreated CD20-positive DLBCL and IPI score must be 2-5
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
General

* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* Contraindication to receive any of the individual components of CHOP, rituximab or obinutuzumab
* Prior anthracycline therapy
* Participants with ongoing corticosteroid use >30 mg per day of prednisone or equivalent
* CNS lymphoma or primary mediastinal DLBCL
* Vaccination with live vaccines within 28 days prior to randomization
* Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
* History of other malignancy that could affect compliance with the protocol or interpretation of results
* Evidence of significant, uncontrolled concomitant disease
* Significant cardiovascular disease or significant pulmonary disease
* Left ventricular ejection fraction less than (<) 50% as defined by multiple-gated acquisition (MUGA)
* 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
* Received the following agents within 7 days prior to the first dose of venetoclax: steroid therapy for anti-neoplastic intent; strong and moderate cytochrome P450 (CYP) 3A4 inhibitors or inducers; grapefruit/grapefruit products, seville oranges or star fruit within 3 days prior to the first dose of venetoclax
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Recent major surgery
* Women who are pregnant or lactating

Dose-Escalation Portion of the Study:

* Participants with confirmed mantle cell lymphoma (MCL) or small lymphocytic lymphoma (SLL)

Expansion Portion of the Study:

* Participants with transformed lymphoma (participants with discordant bone marrow involvement (i.e., low grade histology in bone marrow) may be considered after discussion with the Medical Monitor)
* Prior therapy for NHL

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
Completed
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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New Mexico
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Austria
State/province [7] 0 0
Salzburg
Country [8] 0 0
Austria
State/province [8] 0 0
Wien
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Czechia
State/province [12] 0 0
Brno
Country [13] 0 0
Czechia
State/province [13] 0 0
Hradec Kralove
Country [14] 0 0
Czechia
State/province [14] 0 0
Ostrava - Poruba
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 2
Country [16] 0 0
France
State/province [16] 0 0
Creteil
Country [17] 0 0
France
State/province [17] 0 0
La Roche sur Yon
Country [18] 0 0
France
State/province [18] 0 0
Le Mans
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Montpellier
Country [21] 0 0
France
State/province [21] 0 0
Nantes
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Pierre-Benite
Country [24] 0 0
France
State/province [24] 0 0
Rennes cedex 09
Country [25] 0 0
France
State/province [25] 0 0
Rouen
Country [26] 0 0
France
State/province [26] 0 0
Vandoeuvre-les-nancy
Country [27] 0 0
Hungary
State/province [27] 0 0
Budapest
Country [28] 0 0
Hungary
State/province [28] 0 0
Debrecen
Country [29] 0 0
Italy
State/province [29] 0 0
Campania
Country [30] 0 0
Italy
State/province [30] 0 0
Liguria
Country [31] 0 0
Italy
State/province [31] 0 0
Piemonte
Country [32] 0 0
Italy
State/province [32] 0 0
Sicilia
Country [33] 0 0
Italy
State/province [33] 0 0
Toscana
Country [34] 0 0
Netherlands
State/province [34] 0 0
Amsterdam
Country [35] 0 0
Netherlands
State/province [35] 0 0
Rotterdam
Country [36] 0 0
Netherlands
State/province [36] 0 0
Utrecht
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Zelenetz AD, Salles G, Mason KD, Casulo C, Le Goui... [More Details]