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

Diffuse Large B-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01402440
• Other study ID #: COEB071X2101
• Secondary ID: 2010-024367-41
• Status: Terminated
• Phase: Phase 1
• Start date: November 2011
• Est. completion date: April 2014

Study information

• Verified date: January 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• AEB071

Locations

Country	Name	City	State
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Pierre-Benite Cédex
France	Novartis Investigative Site	Rouen Cedex 1
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Muenchen
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Torino	TO
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Manchester
United States	Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State	Columbus	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	Hackensack University Medical Center Hackensack (SC)	Hackensack	New Jersey
United States	University of Texas/MD Anderson Cancer Center SC Location	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center MSK 2	New York	New York
United States	Washington University School of Medicine Div. of Medical Oncology	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase)		Cycle 1 (28 days)
Primary	Number of Pparticipants reporting Serious Adverse Events and Adverse Events (Dose Expansion phase)		Baseline, 28 days
Secondary	Overall Response Rate, using NHLIWG criteria	Assess the overall response rate to AEB071	Baseline, 12 months
Secondary	Number of Participants reporting Serious Adverse Events and Adverse Events		Baseline, 12 months
Secondary	AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA	Evaluate the single and multiple dose PK of AEB071 in patients with Diffuse Large B-Cell Lymphoma (DLBCL)	First 7 months of treatment period
Secondary	Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071	Assess the pharmacodynamic response to AEB071 in Lymphoma and blood specimens	First 7 months of treatment period

External Links

•   Results for OEB071X2101 can be found on the Novartis Clinical Trial Results Website