The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
RO6870810 subcutaneously (SC) at dose of 0.30, 0.45, or 0.65 milligram per kilogram (mg/kg) on Days 1-14 of 21-day cycles.
Venetoclax tablets orally at dose of 400 mg once daily (QD) continuously for 21 days.
Rituximab intravenously (IV) at dose of 375 mg/m\^2 weekly during the first 21-day cycle (C1) and on day 1 of each cycle thereafter.
City of Hope National Medical Center
Duarte, California, United States
Stanford Cancer Center
Stanford, California, United States
Weill Cornell Medical College
New York, New York, United States
Levine Cancer Institute - Blythe
Charlotte, North Carolina, United States
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia
Rigshospitalet; Hæmatologisk Klinik
København Ø, Denmark
Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
Barcelona, Spain
Hospital Duran i Reynals; Servicio de Hematologia
Barcelona, Spain
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Madrid, Spain
Percentage of Participants With Dose-Limiting Toxiciities (DLT)- Part 1
DLT is defined as any of the toxicities- occurs within the first cycle for which the participant receives the full intended combination doses and number of administrations; is considered to be related to study treatment by the investigator; is not attributed to disease progression or another clearly identifiable cause.
Time frame: Cycle (C) 1 (21 days)
Percentage of Participants With Adverse Events (AEs) - Part 1
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Up to 36 months
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1
Time frame: Up to 36 months
Complete Response (CR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- Recommended Dose (RD) Expansion - Part 2
Time frame: Up to 36 months
Overall Response (OR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- RD Expansion - Part 2
Time frame: Up to 36 months
Percentage of Participants With Adverse Events (AEs) - Part 2
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Up to 36 months
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 2
Time frame: Up to 36 months
Maximum Concentration (Cmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Trough Serum Concentration (Cmin) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Cycle 2 and all other subsequent even Cycles (Up to 36 months)
Time of Maximum Concentration (tmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Clearance (CL) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Volume of Distribution (Vd) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Area Under the Curve (AUC) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Complete Response (CR) Rate as Determined by the Investigator Based on the Modified Lugano Response Criteria- Part 1 and Part 2
Time frame: Up to 36 months
Complete Response (CR) Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Time frame: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of Modified Lugano Response Criteria- Part 1 and Part 2
Time frame: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Time frame: Up to 36 months
Duration of Response (DoR)- Part 1 and Part 2
Time frame: Up to 36 months
Progression-Free Survival (PFS)- Part 1 and Part 2
Time frame: Up to 36 months
Event-Free Survival (EFS)- Part 1 and Part 2
Time frame: Up to 36 months
Disease-Free Survival (DFS)- Part 1 and Part 2
Time frame: Up to 36 months
Overall Survival (OS)- Part 1 and Part 2
Time frame: Up to 36 months
Half-Life (t1/2) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Percentage of Ant-Drug Antibodies (ADA) Against Rituximab - Part 1 and Part 2
Time frame: Pre-dose, End of Infusion Day 1 Cycle 1; Pre-dose Day 1 Cycle 2, 3, 4 , 6 and all other even Cycles (Up to 36 months)
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