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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01854606
First received: May 13, 2013
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma
Drug: AEB071
Drug: Everolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071and EVEROLIMUS combination therapy in patients with DLBCL.

  • 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 ] [ Designated as safety issue: No ]
    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:
  • Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities

  • Best Overall Response (BOR) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  • Duration of Response (DOR) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  • Progression Free survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  • Overall Survival (OS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS

  • Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To characterize the PK profiles of AEB071 and EVEROLIMUS


Estimated Enrollment: 70
Study Start Date: December 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT01854606

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

  Show 29 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01854606     History of Changes
Other Study ID Numbers: COEB071X2103
Study First Received: May 13, 2013
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
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
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014