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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT01402440

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: AEB071	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AEB071	Drug: AEB071

Arm

Intervention/Treatment

Experimental: AEB071

Drug: AEB071

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010-3000
2	Washington University School of Medicine Div. of Medical Oncology	Saint Louis	Missouri	United States	63110
3	Hackensack University Medical Center Hackensack (SC)	Hackensack	New Jersey	United States	07601
4	Memorial Sloan Kettering Cancer Center MSK 2	New York	New York	United States	10021
5	Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State	Columbus	Ohio	United States	43210
6	University of Texas/MD Anderson Cancer Center SC Location	Houston	Texas	United States	77030-4009
7	Novartis Investigative Site	Creteil		France	94010
8	Novartis Investigative Site	Lille Cedex		France	59 037
9	Novartis Investigative Site	Pierre-Benite Cédex		France	F-69495
10	Novartis Investigative Site	Rouen Cedex 1		France	76038
11	Novartis Investigative Site	Berlin		Germany	13353
12	Novartis Investigative Site	Muenchen		Germany	81377
13	Novartis Investigative Site	Shatin, New Territories		Hong Kong
14	Novartis Investigative Site	Milano	MI	Italy	20133
15	Novartis Investigative Site	Torino	TO	Italy	10126
16	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	135-710
17	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
18	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
19	Novartis Investigative Site	Rotterdam		Netherlands	3015 CE
20	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
21	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
22	Novartis Investigative Site	Barcelona		Spain	08025
23	Novartis Investigative Site	Taipei		Taiwan	10048
24	Novartis Investigative Site	Manchester		United Kingdom	M20 2BX