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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01402440
Recruitment Status : Terminated (Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.)
First Posted : July 26, 2011
Last Update Posted : December 19, 2020
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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Study Type : Interventional  (Clinical Trial)
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 : November 2011
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: AEB071 Drug: AEB071

Primary Outcome Measures :
  1. Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase) [ Time Frame: Cycle 1 (28 days) ]
  2. Number of Pparticipants reporting Serious Adverse Events and Adverse Events (Dose Expansion phase) [ Time Frame: Baseline, 28 days ]

Secondary Outcome Measures :
  1. Overall Response Rate, using NHLIWG criteria [ Time Frame: Baseline, 12 months ]
    Assess the overall response rate to AEB071

  2. Number of Participants reporting Serious Adverse Events and Adverse Events [ Time Frame: Baseline, 12 months ]
  3. AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA [ Time Frame: First 7 months of treatment period ]
    Evaluate the single and multiple dose PK of AEB071 in patients with Diffuse Large B-Cell Lymphoma (DLBCL)

  4. Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071 [ Time Frame: First 7 months of treatment period ]
    Assess the pharmacodynamic response to AEB071 in Lymphoma and blood specimens

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01402440

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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
United States, Missouri
Washington University School of Medicine Div. of Medical Oncology
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center Hackensack (SC)
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center MSK 2
New York, New York, United States, 10021
United States, Ohio
Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State
Columbus, Ohio, United States, 43210
United States, Texas
University of Texas/MD Anderson Cancer Center SC Location
Houston, Texas, United States, 77030-4009
Novartis Investigative Site
Creteil, France, 94010
Novartis Investigative Site
Lille Cedex, France, 59 037
Novartis Investigative Site
Pierre-Benite Cédex, France, F-69495
Novartis Investigative Site
Rouen Cedex 1, France, 76038
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Muenchen, Germany, 81377
Hong Kong
Novartis Investigative Site
Shatin, New Territories, Hong Kong
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Torino, TO, Italy, 10126
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08003
Novartis Investigative Site
Barcelona, Spain, 08025
Novartis Investigative Site
Taipei, Taiwan, 10048
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M20 2BX
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novarts Pharmaceuticals Novarts Pharmaceuticals
Additional Information:
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT01402440    
Other Study ID Numbers: COEB071X2101
2010-024367-41 ( EudraCT Number )
First Posted: July 26, 2011    Key Record Dates
Last Update Posted: December 19, 2020
Last Verified: January 2015
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Diffuse Large B-Cell Lymphoma,
Phase 1,
CD79 Mutation
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin