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

NCT01854606 | Completed Phase 1 FDA Drug

• 1 other identifier: COEB071X2103
• Study Type: interventional
• Target: 31
• Locations: 8 countries
• Sites: 15

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.

Conditions

CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma, DBCL, AEB071, Everolimus

Outcome Measures

Primary Outcomes (2)

• Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle

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

  12 months

• Phase II- Overall response rate (ORR) = complete response (CR) + partial response (PR) according to the non-Hodgkin's Lymphoma International Working Group criteria

  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

  12 months

Secondary Outcomes (6)

• Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.

  24 months

• Best Overall Response (BOR)

  24 months

• Duration of Response (DOR)

  24 months

• Progression Free survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

Study Arms (1)

AEB071 and EVEROLIMUS

EXPERIMENTAL

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

Drug: AEB071; Drug: Everolimus

Interventions

AEB071 DRUG

a Protein Kinase C Inhibitor

Also known as: sotrastuarin

AEB071 and EVEROLIMUS

Everolimus DRUG

mTOR inhibitor

Also known as: RAD001

AEB071 and EVEROLIMUS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Washington University School of Medicine Dept of Oncology.

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center Onc. Dept.

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute Dept of Onc

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Rouen, 76038, France

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

New Territories, Hong Kong, Hong Kong

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Links

• Results for COEB071X2103 from the Novartis Clinical Trials website

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

sotrastaurin; Everolimus

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2013
• First Posted: May 15, 2013
• Study Start: December 5, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 19, 2020

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); US (3); HK (2); KR (2); FR (1); IT (2); NL (2); TW (1)