CD79 Mutant or ABC-subtype Diffuse Large B-Cell LymphomaPhase 1COEB071X2103NCT01854606
Safety and Efficacy of AEB071 and EVEROLIMUS in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma
A Phase 1 study testing AEB071 and Everolimus in people with CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma, run by Novartis Pharmaceuticals at 15 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma
- What is being tested?
- AEB071 and Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 15 sitesin 8 countries
- Study dates
- 5 Dec 2013to 1 Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
15 sites in 8 countries.
15 sites in 8 countries
United States3 sites
Sarah Cannon Research Institute Dept of Onc
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center Onc. Dept.
New York, New York, 10065
Washington University School of Medicine Dept of Oncology.
St Louis, Missouri, 63110
Germany2 sites
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
München, 81377
Hong Kong2 sites
Novartis Investigative Site
Hong Kong
Novartis Investigative Site
New Territories, Hong Kong
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Netherlands2 sites
Novartis Investigative Site
Rotterdam, 3015 CE
Novartis Investigative Site
Rotterdam, 3075 EA
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 03080
Novartis Investigative Site
Seoul, Korea, 06351
About this study
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
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.
Read the 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.
- Being tested
- AEB071, Everolimus
- Keywords
- Diffuse Large B-Cell Lymphoma, DBCL, AEB071, Everolimus
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEB071Drug
Also called sotrastuarin
a Protein Kinase C Inhibitor
EverolimusDrug
Also called RAD001
mTOR inhibitor
| Study group | Role | What they receive |
|---|---|---|
| AEB071 and EVEROLIMUS | Experimental | AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study Receives: Drug: AEB071; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 12 months
Secondary outcomes (6)
Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.
Safety and tolerability of AEB071 and EVEROLIMUS, including acute and chronic toxicities
Measured: 24 months
Best Overall Response (BOR)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Measured: 24 months
Duration of Response (DOR)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Measured: 24 months
Progression Free survival (PFS)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Measured: 24 months
Overall Survival (OS)
Evaluate preliminary anti-tumor activity for AE071 and EVEROLIMUS
Measured: 24 months
Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib
To characterize the PK profiles of AEB071 and EVEROLIMUS
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study start5 Dec 2013
- Primary completion1 Jun 2016
- Study completion1 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CD79 Mutant or ABC-subtype Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854606
- Sponsor's protocol ID
- COEB071X2103
- Acronym
- COEB071X2103
- Status last verified
- May 2017
- First submitted
- 13 May 2013
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01854606
- Acronym / sponsor ID
- COEB071X2103 / COEB071X2103
- Keywords
- Diffuse Large B-Cell Lymphoma, DBCL, AEB071, Everolimus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2013 (actual)
- Primary completion
- 1 Jun 2016 (actual)
- Study completion
- 1 Jun 2016 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AEB071 and EVEROLIMUS | Experimental | Drug: AEB071, Drug: EverolimusAEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AEB071Also: sotrastuarina Protein Kinase C Inhibitor | Drug | AEB071 and EVEROLIMUS |
| EverolimusAlso: RAD001mTOR inhibitor | Drug | AEB071 and EVEROLIMUS |
Primary outcome
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.
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
6 secondary outcomes
Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.
Time frame: 24 months
Best Overall Response (BOR)
Time frame: 24 months
Duration of Response (DOR)
Time frame: 24 months
Progression Free survival (PFS)
Time frame: 24 months
Overall Survival (OS)
Time frame: 24 months
Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for COEB071X2103 from the Novartis Clinical Trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AEB071 and Everolimus in people with CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma, run by Novartis Pharmaceuticals at 15 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Germany, Hong Kong, Italy, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.