A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6
- Conditions
- Diffuse Large B-cell LymphomaHigh-Grade B-cell Lymphoma
- Interventions
- Registration Number
- NCT03255096
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Phase (Part 1) RO6870810 Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Expansion Phase (Part 2) RO6870810 Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Expansion Phase (Part 2) Rituximab Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Dose Escalation Phase (Part 1) Venetoclax Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Dose Escalation Phase (Part 1) Rituximab Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Expansion Phase (Part 2) Venetoclax Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1 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 Up to 36 months Percentage of Participants With Adverse Events (AEs) - Part 1 Up to 36 months 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.
Overall Response (OR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- RD Expansion - Part 2 Up to 36 months Percentage of Participants With Dose-Limiting Toxiciities (DLT)- Part 1 Cycle (C) 1 (21 days) 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DoR)- Part 1 and Part 2 Up to 36 months Progression-Free Survival (PFS)- Part 1 and Part 2 Up to 36 months Event-Free Survival (EFS)- Part 1 and Part 2 Up to 36 months Disease-Free Survival (DFS)- Part 1 and Part 2 Up to 36 months Percentage of Participants With Adverse Events (AEs) - Part 2 Up to 36 months 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.
Trough Serum Concentration (Cmin) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 Pre-dose Cycle 2 and all other subsequent even Cycles (Up to 36 months) Clearance (CL) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 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) 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 Up to 36 months Time of Maximum Concentration (tmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 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 Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 2 Up to 36 months Maximum Concentration (Cmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 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 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 ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2 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 Up to 36 months Overall Survival (OS)- Part 1 and Part 2 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 Up to 36 months Percentage of Ant-Drug Antibodies (ADA) Against Rituximab - Part 1 and Part 2 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) Area Under the Curve (AUC) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 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) Half-Life (t1/2) of RO6870810 and its Potential Metabolites- Part 1 and Part 2 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)
Trial Locations
- Locations (9)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Peter MacCallum Cancer Centre-East Melbourne
🇦🇺Melbourne, Victoria, Australia
Levine Cancer Institute - Blythe
🇺🇸Charlotte, North Carolina, United States
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
Weill Cornell Medical College
🇺🇸New York, New York, United States