Safety and Efficacy of AEB071 and EVEROLIMUS in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma (COEB071X2103)

Novartis

Status and phase

Completed

Phase 1

Conditions

CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma

Treatments

Drug: AEB071

Drug: Everolimus

Study type

Interventional

Funder types

Industry

Identifiers

NCT01854606

COEB071X2103

Details and patient eligibility

About

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.

Full 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.

Enrollment

31 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.