Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Diffuse Large B-Cell Lymphoma,, Phase 1,, CD79 Mutation
Brief summary
This study has two phases, a dose escalation phase and a dose expansion phase. For dose escalation, the primary objective is to estimate the maximum tolerated dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoint for this objective will be occurrence of Dose Limiting Toxicity. For dose expansion, the primary objective is to characterize the safety and tolerability of the maximum tolerated dose or recommended phase 2 dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoints for this objective will be occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs), assessment of clinical laboratory values, and vital sign measurements.
Interventions
DRUGAEB071
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase) | Cycle 1 (28 days) |
| Number of Pparticipants reporting Serious Adverse Events and Adverse Events (Dose Expansion phase) | Baseline, 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate, using NHLIWG criteria | Baseline, 12 months | Assess the overall response rate to AEB071 |
| Number of Participants reporting Serious Adverse Events and Adverse Events | Baseline, 12 months | — |
| AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA | First 7 months of treatment period | Evaluate the single and multiple dose PK of AEB071 in patients with Diffuse Large B-Cell Lymphoma (DLBCL) |
| Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071 | First 7 months of treatment period | Assess the pharmacodynamic response to AEB071 in Lymphoma and blood specimens |
Countries
France, Germany, Hong Kong, Italy, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed