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
26 de mayo de 2020 actualizado por: Hoffmann-La Roche
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
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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
267
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
New South Wales
-
Concord, New South Wales, Australia, 2139
- Concord Repatriation General Hospital
-
-
Queensland
-
Woolloongabba, Queensland, Australia, 4102
- Princess Alexandra Hospital
-
-
Victoria
-
Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Centre-East Melbourne
-
Parkville, Victoria, Australia, 3050
- Royal Melbourne Hospital
-
-
-
-
-
Salzburg, Austria, 5020
- Lkh - Universitatsklinikum Der Pmu Salzburg
-
Wien, Austria, 1090
- Medizinische Universität Wien
-
-
-
-
-
Quebec, Canadá, G1J 1Z4
- CHU de Quebec - Hôpital de l' Enfant Jésus
-
-
Alberta
-
Edmonton, Alberta, Canadá, T6G 1Z2
- Cross Cancer Institute
-
-
British Columbia
-
Kelowna, British Columbia, Canadá, V1Y 5L3
- BC Cancer Agency, CSI
-
Vancouver, British Columbia, Canadá, V5Z 4E6
- BC Cancer Agency Vancouver Centre - PARENT; BC Cancer Agency
-
-
Quebec
-
Montréal, Quebec, Canadá, H3T 1E2
- Jewish General Hospital; Research Unit
-
-
-
-
-
Brno, Chequia, 613 00
- Fakultni nemocnice Brno
-
Hradec Kralove, Chequia, 500 05
- Fakultni nemocnice Hradec Kralove
-
Ostrava - Poruba, Chequia, 708 52
- Fakultni nemocnice Ostrava
-
Praha 2, Chequia, 128 08
- Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
-
-
-
-
-
Barcelona, España, 08003
- Hospital del Mar
-
Barcelona, España, 08035
- Hospital Universitari Vall d'Hebron
-
Barcelona, España, 08907
- ICO l´Hospitalet - Hospital Duran i Reynals; Hematology
-
Madrid, España, 28034
- Hospital Universitario Ramón y Cajal
-
Madrid, España, 280146
- Hospital Universitario La Paz
-
Salamanca, España, 37007
- Hospital Universitario de Salamanca
-
-
-
-
California
-
Fullerton, California, Estados Unidos, 92835
- St. Jude Heritage Healthcare
-
Los Angeles, California, Estados Unidos, 90095
- UCLA Jonsson Comprehensive Cancer Center
-
Santa Maria, California, Estados Unidos, 93454
- Central Coast Medical Oncology
-
-
Missouri
-
Saint Louis, Missouri, Estados Unidos, 63129
- The West Clinici
-
-
New Jersey
-
Hackensack, New Jersey, Estados Unidos, 07601
- Hackensack University Medical Center; WFAN - Imus Pediatric Center
-
-
New Mexico
-
Farmington, New Mexico, Estados Unidos, 87401
- San Juan Oncology Associates
-
-
New York
-
New York, New York, Estados Unidos, 10065
- Memorial Sloan-Kettering Cancer Center
-
Rochester, New York, Estados Unidos, 14642
- Uni of Rochester Medical Center; Wilmot Cancer Center, Pharmacy Department
-
-
Tennessee
-
Nashville, Tennessee, Estados Unidos, 37203
- Tennessee Oncology
-
-
-
-
-
Creteil, Francia, 94010
- Hopital Henri Mondor, Unite Hemopathies lymphoides
-
La Roche sur Yon, Francia, 85025
- Centre Hospitalier Departemental Les Oudairies
-
Le Mans, Francia, 72015
- Clinique Victor Hugo; Pharmacie
-
Lille, Francia, 59037
- Hopital Claude Huriez - CHU Lille
-
Montpellier, Francia, 34295
- Hôpital Saint Eloi
-
Nantes, Francia, 44093
- CHU Nantes - Hôtel Dieu; Service Assistance Medicale à la Procreation
-
Paris, Francia, 75475
- Hôpital Saint-Louis
-
Pierre-Benite, Francia, 69495
- Centre Hospitalier Lyon sud
-
Rennes cedex 09, Francia, 35033
- CHU Rennes - Hopital Pontchaillou
-
Rouen, Francia, 76038
- Centre Henri Becquerel; Hematologie
-
Vandoeuvre-les-nancy, Francia, 54511
- Hôpital de Brabois Adultes
-
-
-
-
-
Budapest, Hungría, 1122
- Orszagos Onkologiai Intezet
-
Budapest, Hungría, 1083
- Semmelweis Egyetem
-
Debrecen, Hungría, 4032
- Debreceni Egyetem; Belgyogyaszati Klinika Hematologiai Tanszek
-
-
-
-
Campania
-
Napoli, Campania, Italia, 80131
- Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
-
-
Liguria
-
Genova, Liguria, Italia, 16132
- Azienda Ospedaliero Universitaria San Martino
-
-
Piemonte
-
Torino, Piemonte, Italia, 10126
- Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
-
-
Sicilia
-
Palermo, Sicilia, Italia, 90127
- Azienda Ospedaliera Vincenzo Cervello
-
-
Toscana
-
Pisa, Toscana, Italia, 56100
- Azienda Ospedaliero Universitaria Pisana; U.O. Farmaceutica
-
-
-
-
-
Amsterdam, Países Bajos, 1081 HV
- Amsterdam UMC location VUMC
-
Rotterdam, Países Bajos, 3015 GD
- Erasmus Medisch Centrum
-
Utrecht, Países Bajos, 3508 GA
- UMC Utrecht
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
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.
|
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.
Otros nombres:
Cyclophosphamide 750 milligrams per square meter (mg/m^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.
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).
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.
Vincristine 1.4 mg/m^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.
Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.
|
|
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.
|
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.
Otros nombres:
Cyclophosphamide 750 milligrams per square meter (mg/m^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.
Vincristine 1.4 mg/m^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.
Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.
Rituximab 375 mg/m^2 dose will be administered IV on Day 1 of every 21-day cycle.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)
Periodo de tiempo: 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)
|
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.
|
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)
|
|
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)
Periodo de tiempo: Baseline up to end of treatment (up to approximately 6 months)
|
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
|
Baseline up to end of treatment (up to approximately 6 months)
|
|
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
Periodo de tiempo: Baseline up to end of treatment (up to approximately 6 months)
|
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.
|
Baseline up to end of treatment (up to approximately 6 months)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)
Periodo de tiempo: Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
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) |
Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
|
Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)
Periodo de tiempo: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
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.
|
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
|
Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)
Periodo de tiempo: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
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 |
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
|
Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) Within the Dosing Interval
Periodo de tiempo: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
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.
|
Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)
|
|
Prednisone Plasma PK: AUC
Periodo de tiempo: 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)
|
AUC was determined based on measurement of Predisone concentrations in plasma over time.
|
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)
|
|
Prednisone Plasma PK: Tmax
Periodo de tiempo: 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)
|
Tmax was determined based on measurement of Predisone concentrations in plasma over time.
|
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)
|
|
Prednisone Plasma PK: Cmax
Periodo de tiempo: 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)
|
Cmax was determined based on measurement of Predisone concentrations in plasma over time.
|
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)
|
|
Rituximab PK: Cmax
Periodo de tiempo: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
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.
|
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
|
Rituximab PK: Cmin Within the Dosing Interval
Periodo de tiempo: Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)
|
Cmin was determined using the pre-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose on Day 1 of Cycle 2.
|
Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)
|
|
Obinutuzumab PK: Cmax
Periodo de tiempo: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
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.
|
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
|
Cyclophosphamide PK: Cmax
Periodo de tiempo: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
Cmax was determined using the post-dose Cyclophosphamide plasma concentrations on Cycle 1 Day 1.
|
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
|
Doxorubicin PK: Cmax
Periodo de tiempo: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
Cmax was determined using the post-dose Doxorubicin plasma concentrations.
|
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
|
Vincristine PK: Cmax
Periodo de tiempo: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
Cmax was determined using the post-dose Vincristine plasma concentrations.
|
End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)
|
|
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
Periodo de tiempo: Baseline to end of treatment (up to approximately 6 months)
|
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 |
Baseline to end of treatment (up to approximately 6 months)
|
|
Percentage of Participants Who Are Alive and Without Disease Progression at Month 12
Periodo de tiempo: 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.
|
Month 12
|
|
Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification
Periodo de tiempo: Baseline up to end of treatment (approx. 6 months)
|
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.
|
Baseline up to end of treatment (approx. 6 months)
|
|
Safety: Percentage of Participants With Adverse Events
Periodo de tiempo: Baseline up to approximately 36 months
|
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.
|
Baseline up to approximately 36 months
|
|
Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy
Periodo de tiempo: Baseline up to Cycle 6 (cycle length = 21 days)
|
Maintenance of relative dose intensity was defined as a dose intensity of >/= 90%.
|
Baseline up to Cycle 6 (cycle length = 21 days)
|
|
Relative Dose Intensity of Venetoclax
Periodo de tiempo: Baseline up to Cycle 6 (cycle length = 21 days)
|
Dose intensity was categorized as < 80%, 80% to < 85%, 85% to < 90%, or >/= 90%.
|
Baseline up to Cycle 6 (cycle length = 21 days)
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de noviembre de 2013
Finalización primaria (Actual)
28 de junio de 2017
Finalización del estudio (Actual)
28 de junio de 2019
Fechas de registro del estudio
Enviado por primera vez
4 de febrero de 2014
Primero enviado que cumplió con los criterios de control de calidad
4 de febrero de 2014
Publicado por primera vez (Estimar)
5 de febrero de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
11 de junio de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
26 de mayo de 2020
Última verificación
1 de mayo de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Linfoma
- Linfoma de células B
- Linfoma No Hodgkin
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Agentes antineoplásicos inmunológicos
- Antibióticos, Antineoplásicos
- Ciclofosfamida
- Venetoclax
- Rituximab
- Prednisona
- Doxorrubicina
- Vincristina
- Obinutuzumab
Otros números de identificación del estudio
- GO27878
- 2013-003749-40 (Número EudraCT)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .