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COEB071X2103: Safety and Efficacy of AEB071 and EVEROLIMUS in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01854606
Collaborator
(none)
31
Enrollment
15
Locations
1
Arm
29.9
Actual Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study of the safety and efficacy of AEB071 and EVEROLIMUS in patients with CD79-mutant or ABC subtype Diffuse Large B-Cell Lymphoma.

The trial did not progress into Phase II due to the suboptimal tolerability of the combination treatment of sotrastaurin and everolimus in the Phase Ib part of the study. There were no serious safety concerns associated with this combination.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This is a Phase Ib dose escalation and Phase II study in patients with DLBCL harboring mutations in CD79A/B or of the ABC subtype. Pre-screening for mutations in CD79A/B or the ABC subtype will be required, as it is anticipated that both patient groups may receive clinical benefit from the combination of AEB071 and EVEROLIMUS.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Single-arm, Phase Ib/II Study of AEB071 (a Protein Kinase C Inhibitor) and Everolimus (mTOR Inhibitor) in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma
Actual Study Start Date :
Dec 5, 2013
Actual Primary Completion Date :
Jun 1, 2016
Actual Study Completion Date :
Jun 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: AEB071 and EVEROLIMUS

AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study

Drug: AEB071
a Protein Kinase C Inhibitor
Other Names:
  • sotrastuarin

    • Drug: Everolimus
    mTOR inhibitor
    Other Names:
  • RAD001

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle [12 months]

      Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071and EVEROLIMUS combination therapy in patients with DLBCL.

    2. Phase II- Overall response rate (ORR) = complete response (CR) + partial response (PR) according to the non-Hodgkin's Lymphoma International Working Group criteria [12 months]

      Assess the preliminary evidence for anti-tumor activity at RP2D for AEB071 and EVEROLIMUS in patients with a CD79 mutation and those wild-type for the mutation but of the ABC subtype

    Secondary Outcome Measures

    1. Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements. [24 months]

      Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities

    2. Best Overall Response (BOR) [24 months]

      Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

    3. Duration of Response (DOR) [24 months]

      Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

    4. Progression Free survival (PFS) [24 months]

      Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

    5. Overall Survival (OS) [24 months]

      Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

    6. Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib [24 months]

      To characterize the PK profiles of AEB071 and EVEROLIMUS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female ≥18 years of age.

    • Diffuse DLBCL with activating mutations in CD79 (A or B subunits) or ABC-subtype DLBCL (CD79 wildtype or CD79 mutant). DLBCL that arose from transformed indolent lymphoma is allowed.

    • Prior treatment and relapse following chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible or who did not respond to chemotherapy may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH. There is no limit to number of prior therapies allowed.

    • May be treated with localized radiation as long as measurable or evaluable disease remains at untreated sites.

    • WHO performance status of ≤ 2.

    • A representative FFPE tumor sample must be available for molecular testing along with a corresponding pathology report. An archival tumor sample may be submitted. However, if not available, a new tumor biopsy obtained for the purpose of this study must be submitted instead.

    Exclusion Criteria:

    • Treatment with strong inducers or inhibitors (medications and herbal supplements) of cytochrome P450 3A4/5 (CYP3A4/5), or CYP3A4/5 substrates with a QT prolongation risk that cannot be discontinued at least 7 half-lives (or if the half-life is unknown,14 days) prior to study drug treatment.

    • Impaired cardiac function or clinically significant cardiac diseases.

    • Impairment of GI function or GI disease that could interfere with the absorption of AEB071 or everolimus.

    • Severe systemic infections, current or within the two weeks prior to initiation of AEB071.

    • Kown history of HIV.

    • Poorly controlled diabetes as defined by a fasting serum glucose > 2.0 x ULN.

    • Evidence of current CNS involvement.

    • Significant symptomatic deterioration of lung function.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Dept of Oncology. Saint Louis Missouri United States 63110
    2 Memorial Sloan Kettering Cancer Center Onc. Dept. New York New York United States 10065
    3 Sarah Cannon Research Institute Dept of Onc Nashville Tennessee United States 37203
    4 Novartis Investigative Site Rouen Cedex 1 France 76038
    5 Novartis Investigative Site Mainz Germany 55131
    6 Novartis Investigative Site Muenchen Germany 81377
    7 Novartis Investigative Site Hong Kong Hong Kong
    8 Novartis Investigative Site New Territories Hong Kong
    9 Novartis Investigative Site Milano MI Italy 20133
    10 Novartis Investigative Site Milano MI Italy 20141
    11 Novartis Investigative Site Seoul Korea Korea, Republic of 03080
    12 Novartis Investigative Site Seoul Korea Korea, Republic of 06351
    13 Novartis Investigative Site Rotterdam Netherlands 3015 CE
    14 Novartis Investigative Site Rotterdam Netherlands 3075 EA
    15 Novartis Investigative Site Taipei Taiwan 10002

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01854606
    Other Study ID Numbers:
    • COEB071X2103
    First Posted:
    May 15, 2013
    Last Update Posted:
    Dec 19, 2020
    Last Verified:
    May 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Diffuse Large B-Cell Lymphoma, DBCL, AEB071, Everolimus
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, B-Cell
    Lymphoma, Large B-Cell, Diffuse
    Everolimus

    Study Results

    No Results Posted as of Dec 19, 2020