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

NCT01402440 | Terminated Phase 1

• 2 other identifiers: COEB071X21012010-024367-41
• Study Type: interventional
• Target: 15
• Locations: 10 countries
• Sites: 24

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma,; Phase 1,; CD79 Mutation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Overall Response Rate, using NHLIWG criteria

  Baseline, 12 months

• 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

• Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071

  First 7 months of treatment period

Study Arms (1)

AEB071

EXPERIMENTAL

Drug: AEB071

Interventions

AEB071 DRUG

AEB071

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Washington University School of Medicine Div. of Medical Oncology

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center Hackensack (SC)

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center MSK 2

New York, New York, 10021, United States

Location

Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State

Columbus, Ohio, 43210, United States

Location

University of Texas/MD Anderson Cancer Center SC Location

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Lille, 59 037, France

Location

Novartis Investigative Site

Pierre-Benite Cédex, F-69495, France

Location

Novartis Investigative Site

Rouen, 76038, France

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Shatin, New Territories, Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Seoul, Korea, 135-710, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, 08025, Spain

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

sotrastaurin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novarts Pharmaceuticals

  Novarts Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2011
• First Posted: July 26, 2011
• Study Start: November 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: December 19, 2020

Record last verified: 2015-01

Locations

FR (4); KR (1); IT (2); US (6); TW (1); HK (1); GB (1); DE (2); ES (2); NL (4)