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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01402440
First received: July 5, 2011
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Diffuse Large B-Cell Lymphoma
Drug: AEB071
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

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

Secondary Outcome Measures:
  • Overall Response Rate, using NHLIWG criteria [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    Assess the overall response rate to AEB071

  • Number of Participants reporting Serious Adverse Events and Adverse Events [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: Yes ]
  • AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA [ Time Frame: First 7 months of treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: First 7 months of treatment period ] [ Designated as safety issue: No ]
    Assess the pharmacodynamic response to AEB071 in Lymphoma and blood specimens


Estimated Enrollment: 58
Study Start Date: November 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEB071 Drug: AEB071

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402440

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 25 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novarts Pharmaceuticals Novarts Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01402440     History of Changes
Other Study ID Numbers: COEB071X2101, 2010-024367-41
Study First Received: July 5, 2011
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration
France : AFFSAPS
Germany : BfArM
Netherlands : Medicines Evaluation Board
Italy : Agenzia Italiana del Farmaco

Keywords provided by Novartis:
Diffuse Large B-Cell Lymphoma,
Phase 1,
CD79 Mutation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on August 01, 2014