Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

• Diffuse large B-cell lymphoma (DLBCL) with activating mutations in CD79 (A or B subunits). DLBCL that arose from transformed indolent lymphoma is allowed.

• Prior treatment and relapse following anthracycline-based chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH alone. There is no limit to prior therapy allowed.

  • Patients may be treated with localized radiation to as many as two sites of disease, so long as measurable or evaluable disease remains at untreated sites.
  • Patients may be treated with corticosteriods immediately prior to enrollment and during the course of the study treatment as long as steriod treatment is tapered to a toal daily dosage of 10mg or less of prednisone (or it's equivalent) prior to AEB071 administration
• WHO performance status of ≤2

Exclusion Criteria:

• Patients at screening who are treated with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that can not be discontinued.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of ventricular tachyarrhythmia
• Presence of unstable atrial fibrillation (ventricular response > 100 bpm); Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
• Angina pectoris or acute myocardial infarction ≤ 3 months prior to starting study drug
• Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
• Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma.
• Patients with impairment of GI function or GI disease that could interfere with the absorption of AEB071.

• Patients with a known history of Human Immunodeficiency Virus (HIV)

  • HIV testing is not required as part of this study

• Patients with a known history of active hepatitis B or C infection unless they are on antiviral therapy

  • The determination of active hepatitis status should be as per standard of care at each site
  • Hepatitis B and C testing is not required as part of this study

Time since the last prior therapy for treatment of underlying malignancy**:

• Cytotoxic chemotherapy: ≤ than the duration of the most recent cycle of the previous regimen (with a minimum of 2 weeks for all)
• Biologic therapy (e.g., antibodies): ≤ 4 weeks

• ≤ 5 x t1/2 of a small molecule therapeutic, not otherwise defined above

  **Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia

• Patients with any history of significant coagulopathy or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies.
• Patients having undergone major surgery less than 4 weeks prior to enrollment or that have not fully recovered from prior surgery.
• Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply