Safety and Efficacy of AEB071 and EVEROLIMUS in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma
- Conditions
- CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT01854606
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AEB071 and EVEROLIMUS AEB071 AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study AEB071 and EVEROLIMUS Everolimus AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study
- Primary Outcome Measures
Name Time Method Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle 12 months Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071and EVEROLIMUS combination therapy in patients with DLBCL.
Phase II- Overall response rate (ORR) = complete response (CR) + partial response (PR) according to the non-Hodgkin's Lymphoma International Working Group criteria 12 months 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
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) 24 months Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Overall Survival (OS) 24 months Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements. 24 months Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities
Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib 24 months To characterize the PK profiles of AEB071 and EVEROLIMUS
Best Overall Response (BOR) 24 months Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Progression Free survival (PFS) 24 months Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Trial Locations
- Locations (4)
Memorial Sloan Kettering Cancer Center Onc. Dept.
🇺🇸New York, New York, United States
Washington University School of Medicine Dept of Oncology.
🇺🇸Saint Louis, Missouri, United States
Sarah Cannon Research Institute Dept of Onc
🇺🇸Nashville, Tennessee, United States
Novartis Investigative Site
🇨🇳Taipei, Taiwan