An Open-Label, Single-arm, Phase I Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma
- 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
- 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
- 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
- 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