Study of the safety and efficacy of AEB071 and EVEROLIMUS in patients with CD79-mutant or ABC subtype Diffuse Large B-Cell Lymphoma. The trial did not progress into Phase II due to the suboptimal tolerability of the combination treatment of sotrastaurin and everolimus in the Phase Ib part of the study. There were no serious safety concerns associated with this combination.
This is a Phase Ib dose escalation and Phase II study in patients with DLBCL harboring mutations in CD79A/B or of the ABC subtype. Pre-screening for mutations in CD79A/B or the ABC subtype will be required, as it is anticipated that both patient groups may receive clinical benefit from the combination of AEB071 and EVEROLIMUS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
a Protein Kinase C Inhibitor
mTOR inhibitor
Washington University School of Medicine Dept of Oncology.
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center Onc. Dept.
New York, New York, United States
Sarah Cannon Research Institute Dept of Onc
Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle
Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071and EVEROLIMUS combination therapy in patients with DLBCL.
Time frame: 12 months
Phase II- Overall response rate (ORR) = complete response (CR) + partial response (PR) according to the non-Hodgkin's Lymphoma International Working Group criteria
Assess the preliminary evidence for anti-tumor activity at RP2D for AEB071 and EVEROLIMUS in patients with a CD79 mutation and those wild-type for the mutation but of the ABC subtype
Time frame: 12 months
Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.
Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities
Time frame: 24 months
Best Overall Response (BOR)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Time frame: 24 months
Duration of Response (DOR)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Time frame: 24 months
Progression Free survival (PFS)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Time frame: 24 months
Overall Survival (OS)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
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Nashville, Tennessee, United States
Novartis Investigative Site
Rouen, France
Novartis Investigative Site
Mainz, Germany
Novartis Investigative Site
München, Germany
Novartis Investigative Site
New Territories, Hong Kong, Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Milan, MI, Italy
...and 5 more locations
Time frame: 24 months
Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib
To characterize the PK profiles of AEB071 and EVEROLIMUS
Time frame: 24 months