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

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ClinicalTrials.gov Identifier: NCT01854606
Recruitment Status : Completed
First Posted : May 15, 2013
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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
CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma Drug: AEB071 Drug: Everolimus 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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
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 : December 5, 2013
Actual Primary Completion Date : June 1, 2016
Actual Study Completion Date : June 1, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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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 Name: sotrastuarin

Drug: Everolimus
mTOR inhibitor
Other Name: RAD001


Outcome Measures
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Primary Outcome Measures :
  1. Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 24 months ]
    Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities

  2. Best Overall Response (BOR) [ Time Frame: 24 months ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  3. Duration of Response (DOR) [ Time Frame: 24 months ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  4. Progression Free survival (PFS) [ Time Frame: 24 months ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  5. Overall Survival (OS) [ Time Frame: 24 months ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  6. Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib [ Time Frame: 24 months ]
    To characterize the PK profiles of AEB071 and EVEROLIMUS


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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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 ClinicalTrials.gov identifier (NCT number): NCT01854606


Locations
United States, Missouri
Washington University School of Medicine Dept of Oncology.
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center Onc. Dept.
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute Dept of Onc
Nashville, Tennessee, United States, 37203
France
Novartis Investigative Site
Rouen Cedex 1, France, 76038
Germany
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Muenchen, Germany, 81377
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
New Territories, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Milano, MI, Italy, 20141
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Netherlands
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
Taiwan
Novartis Investigative Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Additional Information:
Results for COEB071X2103 from the Novartis Clinical Trials website  This link exits the ClinicalTrials.gov site

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01854606     History of Changes
Other Study ID Numbers: COEB071X2103
First Posted: May 15, 2013    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
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 ( Novartis Pharmaceuticals ):
Diffuse Large B-Cell Lymphoma, DBCL, AEB071, Everolimus

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
 Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents