This trial has been completed.

Condition cd79 mutant or abc-subtype diffuse large b-cell lymphoma
Treatments aeb071, everolimus
Phase phase 1/phase 2
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date December 2013
End date June 2016
Trial size 31 participants
Trial identifier NCT01854606, COEB071X2103


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model single group assignment
Primary purpose treatment
Masking no masking
AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study
aeb071 sotrastuarin
a Protein Kinase C Inhibitor
everolimus RAD001
mTOR inhibitor

Primary Outcomes

Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle
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
time frame: 12 months

Secondary Outcomes

Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.
time frame: 24 months
Best Overall Response (BOR)
time frame: 24 months
Duration of Response (DOR)
time frame: 24 months
Progression Free survival (PFS)
time frame: 24 months
Overall Survival (OS)
time frame: 24 months
Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib
time frame: 24 months

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Male or female ≥18 years of age. - Diffuse DLBCL with activating mutations in CD79 (A or B subunits) or ABC-subtype DLBCL (CD79 wildtype or CD79 mutant). DLBCL that arose from transformed indolent lymphoma is allowed. - Prior treatment and relapse following chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible or who did not respond to chemotherapy may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH. There is no limit to number of prior therapies allowed. - May be treated with localized radiation as long as measurable or evaluable disease remains at untreated sites. - WHO performance status of ≤ 2. - A representative FFPE tumor sample must be available for molecular testing along with a corresponding pathology report. An archival tumor sample may be submitted. However, if not available, a new tumor biopsy obtained for the purpose of this study must be submitted instead. Exclusion Criteria: - Treatment with strong inducers or inhibitors (medications and herbal supplements) of cytochrome P450 3A4/5 (CYP3A4/5), or CYP3A4/5 substrates with a QT prolongation risk that cannot be discontinued at least 7 half-lives (or if the half-life is unknown,14 days) prior to study drug treatment. - Impaired cardiac function or clinically significant cardiac diseases. - Impairment of GI function or GI disease that could interfere with the absorption of AEB071 or everolimus. - Severe systemic infections, current or within the two weeks prior to initiation of AEB071. - Kown history of HIV. - Poorly controlled diabetes as defined by a fasting serum glucose > 2.0 x ULN. - Evidence of current CNS involvement. - Significant symptomatic deterioration of lung function.

Additional Information

Official title An Open-Label, Single-arm, Phase Ib/II Study of AEB071 (a Protein Kinase C Inhibitor) and Everolimus (mTOR Inhibitor) in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2017.
Information provided to ClinicalTrials.gov by Novartis.