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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

Primary Purpose

Lymphoma, Non-Hodgkin

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Venetoclax

Cyclophosphamide

Obinutuzumab

Rituximab

Doxorubicin

Vincristine

Prednisone

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

General Inclusion Criteria:

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

Exclusion Criteria:

General Exclusion Criteria:

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

Sites / Locations

St. Jude Heritage Healthcare
UCLA Jonsson Comprehensive Cancer Center
Central Coast Medical Oncology
The West Clinici
Hackensack University Medical Center; WFAN - Imus Pediatric Center
San Juan Oncology Associates
Memorial Sloan-Kettering Cancer Center
Uni of Rochester Medical Center; Wilmot Cancer Center, Pharmacy Department
Tennessee Oncology
Concord Repatriation General Hospital
Princess Alexandra Hospital
Peter MacCallum Cancer Centre-East Melbourne
Royal Melbourne Hospital
LKH - Universitätsklinikum der PMU Salzburg
Medizinische Universität Wien
Cross Cancer Institute
BC Cancer Agency, CSI
BC Cancer Agency Vancouver Centre - PARENT; BC Cancer Agency
Jewish General Hospital; Research Unit
CHU de Quebec - Hôpital de l' Enfant Jésus
Fakultni nemocnice Brno
Fakultni nemocnice Hradec Kralove
Fakultni nemocnice Ostrava
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
Hopital Henri Mondor, Unite Hemopathies lymphoides
Centre Hospitalier Départemental Les Oudairies
Clinique Victor Hugo; Pharmacie
Hopital Claude Huriez - CHU Lille
Hopital Saint Eloi
CHU Nantes - Hôtel Dieu; Service Assistance Medicale à la Procreation
Hôpital Saint-Louis
Centre Hospitalier Lyon Sud
CHU Rennes - Hopital Pontchaillou
Centre Henri Becquerel; Hematologie
Hôpital de Brabois Adultes
Semmelweis Egyetem
Orszagos Onkologiai Intezet
Debreceni Egyetem; Belgyogyaszati Klinika Hematologiai Tanszek
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
Azienda Ospedaliero Universitaria San Martino
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Azienda Ospedaliera Vincenzo Cervello
Azienda Ospedaliero Universitaria Pisana; U.O. Farmaceutica
Amsterdam UMC Location VUMC
Erasmus Medisch Centrum
UMC Utrecht
Hospital del Mar
Hospital Universitari Vall d'Hebron
ICO l´Hospitalet - Hospital Duran i Reynals; Hematology
Hospital Universitario La Paz
Hospital Universitario Ramon y Cajal
Hospital Universitario de Salamanca

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Venetoclax + G-CHOP Arm

Venetoclax + R-CHOP Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)

DLTs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Decrease in B cells, lymphopenia, and leukopenia caused by lymphopenia were not considered DLTs but instead were expected outcomes of study treatment. Any Grade >/= 3 adverse event, that was attributed to having a reasonable possibility of being related to the combined administration of venetoclax plus R-CHOP or G-CHOP, that could not be attributed by the investigator to an alternative, clearly identifiable cause such as tumor progression, concurrent illness or medical condition, or concomitant medication and that occurred during the DLT observation period (start of venetoclax treatment through end of Cycle 2) was considered a DLT for dose-escalation purposes. Grade 3 or 4 neutropenia or thrombocytopenia identified on Day 1 of Cycle 2 or 3, resulting in dose delay were considered DLTs.

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)

CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake </= mediastinum; 3) uptake < mediastinum but </= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy

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

Secondary Outcome Measures

Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)

AUC was calculated based on measurement of venetoclax concentration in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as hour*micrograms per milliliter (hr*mcg/mL)

Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)

Tmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)

Cmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as micrograms per milliliter

Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) Within the Dosing Interval

Cmin was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Prednisone Plasma PK: AUC

AUC was determined based on measurement of Predisone concentrations in plasma over time.

Prednisone Plasma PK: Tmax

Tmax was determined based on measurement of Predisone concentrations in plasma over time.

Prednisone Plasma PK: Cmax

Cmax was determined based on measurement of Predisone concentrations in plasma over time.

Rituximab PK: Cmax

Cmax was determined using the post-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Rituximab PK: Cmin Within the Dosing Interval

Cmin was determined using the pre-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose on Day 1 of Cycle 2.

Obinutuzumab PK: Cmax

Cmax was determined using the post-dose obinutuzumab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Cyclophosphamide PK: Cmax

Cmax was determined using the post-dose Cyclophosphamide plasma concentrations on Cycle 1 Day 1.

Doxorubicin PK: Cmax

Cmax was determined using the post-dose Doxorubicin plasma concentrations.

Vincristine PK: Cmax

Cmax was determined using the post-dose Vincristine plasma concentrations.

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

Objective Response defined as PR (partial response) or CR (complete response) at end of treatment. CR: Lymph nodes and extra-lymphatic sites with score 1, 2 or 3 on a 5-point scale (with a higher score being a worse outcome). No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: Lymph nodes and extralymphatic sites with score of 4 or 5 on the 5-point scale with reduced uptake compared with baseline and residual mass(es) of any size. CT-based response criteria for PR must also be met. No new lesions. In bone marrow residual uptake could be higher than in normal marrow but must be reduced compared with baseline; persistent focal changes in the marrow to be considered for further evaluation with magnetic resonance imaging (MRI) or biopsy or an interval scan. OR=PR+CR

Percentage of Participants Who Are Alive and Without Disease Progression at Month 12

Progressive disease (PD) was determined using the modified Lugano classification criteria. For PET-CT-based PD: Score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver and/or new lesions) with an increase in intensity of uptake from baseline in target nodes and nodal lesions, new FDG-uptake foci of extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment, no non-measured lesions, new FDG-uptake foci consistent with lymphoma, new or recurrent FDG-uptake foci in bone marrow. For CT-based PD: >/= 50% decrease in SPD of up to 6 target measureable nodes and extranodal sites; non-measured lesion should be absent/normal, have regressed, but not increased; no new lesions.

Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification

CR was defined as follows according to modified Lugano classification for CT-based response: Target nodes/nodal masses must have regressed to </= 1.5 cm in longest transverse diameter of a lesion (LDi), no extra-lymphatic sites of disease, absence of non-measured lesions, organ enlargement must have regressed to normal, no new lesions, and if the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

Safety: Percentage of Participants With Adverse Events

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy

Maintenance of relative dose intensity was defined as a dose intensity of >/= 90%.

Relative Dose Intensity of Venetoclax

Dose intensity was categorized as < 80%, 80% to < 85%, 85% to < 90%, or >/= 90%.

Full Information

NCT ID

NCT02055820

First Posted

February 4, 2014

Last Updated

May 26, 2020

Sponsor

Hoffmann-La Roche

Collaborators

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02055820

Brief 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

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

November 17, 2013 (Actual)

Primary Completion Date

June 28, 2017 (Actual)

Study Completion Date

June 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

Collaborators

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is a multicenter, open-label, dose-finding study of venetoclax administered orally in combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide, doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's Lymphoma (NHL). The study consisted of 2 stages: a dose-finding Phase Ib stage and a Phase II expansion stage. In the Phase I portion of the study, participants were randomized to one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in combination with G-CHOP (Arm B) and explored the doses of venetoclax in combination with R-CHOP and G-CHOP. The maximum tolerated dose (MTD) of venetoclax in combination with R-CHOP and G-CHOP was determined during the dose-finding stage. For the Phase II portion of the study, the venetoclax dose for venetoclax + R-CHOP was on a non-continuous dosing schedule as determined by the Phase Ib portion of the study based on safety and tolerability observed in participants treated in the dose escalation portion of the study. On 17 July 2016, Roche/Genentech as the sponsor of Study BO21005 (Goya study), a Phase III study that evaluated G CHOP versus R-CHOP in 1L DLBCL, informed through a press release that the primary endpoint of investigator-assessed PFS was not met. Given these results, Arm B (venetoclax + G-CHOP) was not expanded in Phase II in patients who are first-line with DLBCL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Non-Hodgkin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

267 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Venetoclax + G-CHOP Arm

Arm Type

Experimental

Arm Description

Arm Title

Venetoclax + R-CHOP Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Other Intervention Name(s)

GDC-0199, ABT-199

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Obinutuzumab

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

MabThera/Rituxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)

Description

Time Frame

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)

Title

Description

Time Frame

Baseline up to end of treatment (up to approximately 6 months)

Title

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

Description

Time Frame

Baseline up to end of treatment (up to approximately 6 months)

Secondary Outcome Measure Information:

Title

Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)

Description

Time Frame

Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)

Title

Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)

Description

Tmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Time Frame

Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Title

Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)

Description

Time Frame

Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Title

Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) Within the Dosing Interval

Description

Cmin was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Time Frame

Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Title

Prednisone Plasma PK: AUC

Description

AUC was determined based on measurement of Predisone concentrations in plasma over time.

Time Frame

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)

Title

Prednisone Plasma PK: Tmax

Description

Tmax was determined based on measurement of Predisone concentrations in plasma over time.

Time Frame

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)

Title

Prednisone Plasma PK: Cmax

Description

Cmax was determined based on measurement of Predisone concentrations in plasma over time.

Time Frame

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)

Title

Rituximab PK: Cmax

Description

Cmax was determined using the post-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Time Frame

End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Title

Rituximab PK: Cmin Within the Dosing Interval

Description

Cmin was determined using the pre-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose on Day 1 of Cycle 2.

Time Frame

Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)

Title

Obinutuzumab PK: Cmax

Description

Cmax was determined using the post-dose obinutuzumab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Time Frame

End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Title

Cyclophosphamide PK: Cmax

Description

Cmax was determined using the post-dose Cyclophosphamide plasma concentrations on Cycle 1 Day 1.

Time Frame

End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Title

Doxorubicin PK: Cmax

Description

Cmax was determined using the post-dose Doxorubicin plasma concentrations.

Time Frame

End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Title

Vincristine PK: Cmax

Description

Cmax was determined using the post-dose Vincristine plasma concentrations.

Time Frame

End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Title

Description

Time Frame

Baseline to end of treatment (up to approximately 6 months)

Title

Percentage of Participants Who Are Alive and Without Disease Progression at Month 12

Description

Time Frame

Month 12

Title

Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification

Description

Time Frame

Baseline up to end of treatment (approx. 6 months)

Title

Safety: Percentage of Participants With Adverse Events

Description

Time Frame

Baseline up to approximately 36 months

Title

Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy

Description

Maintenance of relative dose intensity was defined as a dose intensity of >/= 90%.

Time Frame

Baseline up to Cycle 6 (cycle length = 21 days)

Title

Relative Dose Intensity of Venetoclax

Description

Dose intensity was categorized as < 80%, 80% to < 85%, 85% to < 90%, or >/= 90%.

Time Frame

Baseline up to Cycle 6 (cycle length = 21 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: General Inclusion Criteria: 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 Exclusion Criteria: General Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

St. Jude Heritage Healthcare

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Facility Name

UCLA Jonsson Comprehensive Cancer Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Central Coast Medical Oncology

City

Santa Maria

State/Province

California

ZIP/Postal Code

93454

Country

United States

Facility Name

The West Clinici

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63129

Country

United States

Facility Name

Hackensack University Medical Center; WFAN - Imus Pediatric Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

San Juan Oncology Associates

City

Farmington

State/Province

New Mexico

ZIP/Postal Code

87401

Country

United States

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Uni of Rochester Medical Center; Wilmot Cancer Center, Pharmacy Department

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

Tennessee Oncology

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Concord Repatriation General Hospital

City

Concord

State/Province

New South Wales

ZIP/Postal Code

2139

Country

Australia

Facility Name

Princess Alexandra Hospital

City

Woolloongabba

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Facility Name

Peter MacCallum Cancer Centre-East Melbourne

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Royal Melbourne Hospital

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3050

Country

Australia

Facility Name

LKH - Universitätsklinikum der PMU Salzburg

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

Medizinische Universität Wien

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Cross Cancer Institute

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Facility Name

BC Cancer Agency, CSI

City

Kelowna

State/Province

British Columbia

ZIP/Postal Code

V1Y 5L3

Country

Canada

Facility Name

BC Cancer Agency Vancouver Centre - PARENT; BC Cancer Agency

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

Facility Name

Jewish General Hospital; Research Unit

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H3T 1E2

Country

Canada

Facility Name

CHU de Quebec - Hôpital de l' Enfant Jésus

City

Quebec

ZIP/Postal Code

G1J 1Z4

Country

Canada

Facility Name

Fakultni nemocnice Brno

City

Brno

ZIP/Postal Code

613 00

Country

Czechia

Facility Name

Fakultni nemocnice Hradec Kralove

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czechia

Facility Name

Fakultni nemocnice Ostrava

City

Ostrava - Poruba

ZIP/Postal Code

708 52

Country

Czechia

Facility Name

Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK

City

Praha 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Hopital Henri Mondor, Unite Hemopathies lymphoides

City

Creteil

ZIP/Postal Code

94010

Country

France

Facility Name

Centre Hospitalier Départemental Les Oudairies

City

La Roche sur Yon

ZIP/Postal Code

85025

Country

France

Facility Name

Clinique Victor Hugo; Pharmacie

City

Le Mans

ZIP/Postal Code

72015

Country

France

Facility Name

Hopital Claude Huriez - CHU Lille

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Hopital Saint Eloi

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

CHU Nantes - Hôtel Dieu; Service Assistance Medicale à la Procreation

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

Hôpital Saint-Louis

City

Paris

ZIP/Postal Code

75475

Country

France

Facility Name

Centre Hospitalier Lyon Sud

City

Pierre-Benite

ZIP/Postal Code

69495

Country

France

Facility Name

CHU Rennes - Hopital Pontchaillou

City

Rennes cedex 09

ZIP/Postal Code

35033

Country

France

Facility Name

Centre Henri Becquerel; Hematologie

City

Rouen

ZIP/Postal Code

76038

Country

France

Facility Name

Hôpital de Brabois Adultes

City

Vandoeuvre-les-nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Semmelweis Egyetem

City

Budapest

ZIP/Postal Code

1083

Country

Hungary

Facility Name

Orszagos Onkologiai Intezet

City

Budapest

ZIP/Postal Code

1122

Country

Hungary

Facility Name

Debreceni Egyetem; Belgyogyaszati Klinika Hematologiai Tanszek

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale

City

Napoli

State/Province

Campania

ZIP/Postal Code

80131

Country

Italy

Facility Name

Azienda Ospedaliero Universitaria San Martino

City

Genova

State/Province

Liguria

ZIP/Postal Code

16132

Country

Italy

Facility Name

Azienda Ospedaliera Città della Salute e della Scienza di Torino

City

Torino

State/Province

Piemonte

ZIP/Postal Code

10126

Country

Italy

Facility Name

Azienda Ospedaliera Vincenzo Cervello

City

Palermo

State/Province

Sicilia

ZIP/Postal Code

90127

Country

Italy

Facility Name

Azienda Ospedaliero Universitaria Pisana; U.O. Farmaceutica

City

Pisa

State/Province

Toscana

ZIP/Postal Code

56100

Country

Italy

Facility Name

Amsterdam UMC Location VUMC

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

Erasmus Medisch Centrum

City

Rotterdam

ZIP/Postal Code

3015 GD

Country

Netherlands

Facility Name

UMC Utrecht

City

Utrecht

ZIP/Postal Code

3508 GA

Country

Netherlands

Facility Name

Hospital del Mar

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

ICO l´Hospitalet - Hospital Duran i Reynals; Hematology

City

Barcelona

ZIP/Postal Code

08907

Country

Spain

Facility Name

Hospital Universitario La Paz

City

Madrid

ZIP/Postal Code

280146

Country

Spain

Facility Name

Hospital Universitario Ramon y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Hospital Universitario de Salamanca

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

30850381

Citation

Zelenetz AD, Salles G, Mason KD, Casulo C, Le Gouill S, Sehn LH, Tilly H, Cartron G, Chamuleau MED, Goy A, Tam CS, Lugtenburg PJ, Petrich AM, Sinha A, Samineni D, Herter S, Ingalla E, Szafer-Glusman E, Klein C, Sampath D, Kornacker M, Mobasher M, Morschhauser F. Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial. Blood. 2019 May 2;133(18):1964-1976. doi: 10.1182/blood-2018-11-880526. Epub 2019 Mar 8.

Results Reference

result

PubMed Identifier

34822104

Citation

Samineni D, Huang W, Gibiansky L, Ding H, Zhang R, Li C, Sinha A, Rajwanshi R, Humphrey K, Bazeos A, Salem AH, Miles D. Population Pharmacokinetics and Exposure-Response Analyses for Venetoclax in Combination with R-CHOP in Relapsed/Refractory and Previously Untreated Patients with Diffuse Large B Cell Lymphoma. Adv Ther. 2022 Jan;39(1):598-618. doi: 10.1007/s12325-021-01919-z. Epub 2021 Nov 25.

Results Reference

derived

PubMed Identifier

33538797

Citation

Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illes A, Johnson NA, Larouche JF, Lugtenburg PJ, Patti C, Salles GA, Trneny M, de Vos S, Mir F, Samineni D, Kim SY, Jiang Y, Punnoose E, Sinha A, Clark E, Spielewoy N, Humphrey K, Bazeos A, Zelenetz AD. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021 Feb 4;137(5):600-609. doi: 10.1182/blood.2020006578. Erratum In: Blood. 2021 Apr 1;137(13):1844.

Results Reference

derived

Learn more about this trial

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

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