Diffuse Large B-Cell LymphomaPhase 1NCT01402440
Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma
A Phase 1 study testing AEB071 in people with Diffuse Large B-Cell Lymphoma, run by Novartis Pharmaceuticals at 24 sites in 10 countries.
Trial summary
This study has two phases, a dose escalation phase and a dose expansion phase. For dose escalation, the primary objective is to estimate the maximum tolerated dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoint for this objective will be occurrence of Dose Limiting Toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- AEB071
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 24 sitesin 10 countries
- Study dates
- Nov 2011to Apr 2014
- 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
- Diffuse large B-cell lymphoma (DLBCL) with activating mutations in CD79 (A or B subunits). DLBCL that arose from transformed indolent lymphoma is allowed.
- Prior treatment and relapse following anthracycline-based chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH alone. There is no limit to prior therapy allowed.
- Patients may be treated with localized radiation to as many as two sites of disease, so long as measurable or evaluable disease remains at untreated sites.
- Patients may be treated with corticosteriods immediately prior to enrollment and during the course of the study treatment as long as steriod treatment is tapered to a toal daily dosage of 10mg or less of prednisone (or it's equivalent) prior to AEB071 administration
- WHO performance status of ≤2
Who cannot join
- Patients at screening who are treated with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that can not be discontinued.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of ventricular tachyarrhythmia
- Presence of unstable atrial fibrillation (ventricular response > 100 bpm); Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
- Angina pectoris or acute myocardial infarction ≤ 3 months prior to starting study drug
- Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
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- Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma.
- Patients with impairment of GI function or GI disease that could interfere with the absorption of AEB071.
- Patients with a known history of Human Immunodeficiency Virus (HIV)
- HIV testing is not required as part of this study
- Patients with a known history of active hepatitis B or C infection unless they are on antiviral therapy
- The determination of active hepatitis status should be as per standard of care at each site
- Hepatitis B and C testing is not required as part of this study
- Time since the last prior therapy for treatment of underlying malignancy:
- Cytotoxic chemotherapy: ≤ than the duration of the most recent cycle of the previous regimen (with a minimum of 2 weeks for all)
- Biologic therapy (e.g., antibodies): ≤ 4 weeks
- ≤ 5 x t1/2 of a small molecule therapeutic, not otherwise defined above
- Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia
- Patients with any history of significant coagulopathy or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies.
- Patients having undergone major surgery less than 4 weeks prior to enrollment or that have not fully recovered from prior surgery.
- Pregnant or nursing (lactating) women
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
24 sites in 10 countries.
24 sites in 10 countries
United States6 sites
Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State
Columbus, Ohio, 43210
City of Hope National Medical Center
Duarte, California, 91010-3000
Hackensack University Medical Center Hackensack (SC)
Hackensack, New Jersey, 07601
University of Texas/MD Anderson Cancer Center SC Location
Houston, Texas, 77030-4009
Memorial Sloan Kettering Cancer Center MSK 2
New York, New York, 10021
Washington University School of Medicine Div. of Medical Oncology
St Louis, Missouri, 63110
France4 sites
Novartis Investigative Site
Créteil, 94010
Novartis Investigative Site
Lille, 59 037
Novartis Investigative Site
Pierre-Benite Cédex, F-69495
Novartis Investigative Site
Rouen, 76038
Netherlands4 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Groningen, 9713 GZ
Novartis Investigative Site
Rotterdam, 3015 CE
Novartis Investigative Site
Rotterdam, 3075 EA
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
München, 81377
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Torino, TO, 10126
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, 08025
Hong Kong1 site
Novartis Investigative Site
Shatin, New Territories, Hong Kong
About this study
Official title: An Open-Label, Single-arm, Phase I Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma
This study has two phases, a dose escalation phase and a dose expansion phase. For dose escalation, the primary objective is to estimate the maximum tolerated dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoint for this objective will be occurrence of Dose Limiting Toxicity. For dose expansion, the primary objective is to characterize the safety and tolerability of the maximum tolerated dose or recommended phase 2 dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoints for this objective will be occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs), assessment of clinical laboratory values, and vital sign measurements.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- AEB071
- Keywords
- Diffuse Large B-Cell Lymphoma,, Phase 1,, CD79 Mutation
- 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
| Study group | Role | What they receive |
|---|---|---|
| AEB071 | Experimental | Not described Receives: Drug: AEB071 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase)
Measured: Cycle 1 (28 days)
Number of Pparticipants reporting Serious Adverse Events and Adverse Events (Dose Expansion phase)
Measured: Baseline, 28 days
Secondary outcomes (4)
Overall Response Rate, using NHLIWG criteria
Assess the overall response rate to AEB071
Measured: Baseline, 12 months
Number of Participants reporting Serious Adverse Events and Adverse Events
Measured: Baseline, 12 months
AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA
Evaluate the single and multiple dose PK of AEB071 in patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Measured: First 7 months of treatment period
Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071
Assess the pharmacodynamic response to AEB071 in Lymphoma and blood specimens
Measured: First 7 months of treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startNov 2011
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsNovarts Pharmaceuticals, Study director, Novarts Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402440
- Sponsor's protocol ID
- COEB071X2101
- Other IDs
- 2010-024367-41
- Status last verified
- Jan 2015
- First submitted
- 5 Jul 2011
- Last updated
- 19 Dec 2020
- Results posted
- 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 I Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01402440
- Acronym / sponsor ID
- COEB071X2101
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- Diffuse Large B-Cell Lymphoma,, Phase 1,, CD79 Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 26 Jul 2011 (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.
This study has two phases, a dose escalation phase and a dose expansion phase. For dose escalation, the primary objective is to estimate the maximum tolerated dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoint for this objective will be occurrence of Dose Limiting Toxicity. For dose expansion, the primary objective is to characterize the safety and tolerability of the maximum tolerated dose or recommended phase 2 dose of AEB071 in patients with diffuse large b-cell lymphoma. The endpoints for this objective will be occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs), assessment of clinical laboratory values, and vital sign measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AEB071 | Experimental | Drug: AEB071 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diffuse large B-cell lymphoma (DLBCL) with activating mutations in CD79 (A or B subunits). DLBCL that arose from transformed indolent lymphoma is allowed.
- Prior treatment and relapse following anthracycline-based chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH alone. There is no limit to prior therapy allowed.
- WHO performance status of ≤2
Key exclusion criteria (22 listed)
- Patients at screening who are treated with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that can not be discontinued.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of ventricular tachyarrhythmia
- Presence of unstable atrial fibrillation (ventricular response > 100 bpm); Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
- Angina pectoris or acute myocardial infarction ≤ 3 months prior to starting study drug
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 |
|---|---|---|
| AEB071 | Drug | AEB071 |
Primary outcome
Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase)
Time frame: Cycle 1 (28 days)
Number of Pparticipants reporting Serious Adverse Events and Adverse Events (Dose Expansion phase)
Time frame: Baseline, 28 days
4 secondary outcomes
Overall Response Rate, using NHLIWG criteria
Time frame: Baseline, 12 months
Number of Participants reporting Serious Adverse Events and Adverse Events
Time frame: Baseline, 12 months
AEB071 PK parameters including Cmax, tmax, AUCt, Ctrough, CL/F and RA
Time frame: First 7 months of treatment period
Pre and post-dose gene and protein expression of cytokines and any correlations with exposure to AEB071
Time frame: First 7 months of treatment period
Results and safety
The study was stopped early (reason given: Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for OEB071X2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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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
Novarts Pharmaceuticals study director
Novarts Pharmaceuticals
24 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AEB071 in people with Diffuse Large B-Cell Lymphoma, run by Novartis Pharmaceuticals at 24 sites in 10 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 5 inclusion and 22 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: stopped early, 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 24 sites in United States, France, Netherlands, Germany, Italy and 5 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 was stopped early (reason given: Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.). Results are not available in the source record.
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?
Frequency of Dose Limiting Toxicity (DLT) during cycle 1 (Dose Escalation phase) (time frame: Cycle 1 (28 days)). 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.