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 September 2014 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01854606
First received: May 13, 2013
Last updated: September 4, 2014
Last verified: September 2014
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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
Show 29 Study Locations
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: | September 4, 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, B-Cell Lymphoma, Large B-Cell, Diffuse Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Everolimus |
Sirolimus Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antineoplastic Agents Immunologic Factors Immunosuppressive Agents Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015