Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular LymphomaPhase 2NCT01693614
Safety and Efficacy of BKM120 in Relapsed and Refractory NHL
A Phase 2 study testing Buparlisib in people with Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, run by Novartis Pharmaceuticals at 20 sites in 8 countries.
Trial summary
This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma
- What is being tested?
- Buparlisib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 20 sitesin 8 countries
- Study dates
- 28 Feb 2013to 21 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma.
- Patient had relapsed or refractory disease and received at least one prior therapy.
- Patient with diffuse large B cell lymphoma had received or was ineligible for autologous or allogeneic stem cell transplant.
- Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the long axis at baseline, then the patient must have had at least one measurable extra-nodal lesion.
- Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Patient had adequate bone marrow and organ function.
Who cannot join
- Patient had received previous treatment with PI3K inhibitors
- Patient had evidence of graft versus host disease (GVHD).
- Patient had active or history of central nervous system (CNS) disease.
- Patient had a concurrent malignancy or had a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer).
- Patient had a score ≥ 12 on the PHQ-9 questionnaire.
- Patient had a GAD-7 mood scale score ≥ 15.
- Pregnant or nursing women
- Patient who did not use highly effective contraception methods to avoid becoming pregnant or conceiving offspring.
Trial locations and contacts
20 sites in 8 countries.
20 sites in 8 countries
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Medical University of South Carolina -Hollings Cancer Center Medical Univ of South Carolina
Charleston, South Carolina, 29425
University of Texas MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)
Houston, Texas, 77030
Memorial Sloan Kettering Dept of Onc.
New York, New York, 10017
University of Nebraska Medical Center Univ Nebraska
Omaha, Nebraska, 68198
France3 sites
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Pierre-Bénite, 69495
Novartis Investigative Site
Rennes, 35019
Belgium2 sites
Novartis Investigative Site
Bruges, 8000
Novartis Investigative Site
Yvoir, 5530
Germany2 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Würzburg, 97080
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
South Korea2 sites
Novartis Investigative Site
Gyeonggi-do, Korea, 10408
Novartis Investigative Site
Seoul, Korea, 06351
Spain2 sites
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Salamanca, Castille and León, 37007
Turkey (Türkiye)2 sites
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Samsun, 55139
About this study
Official title: An Open-label Phase II Study of BKM120 in Subjects With Relapsed and Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma and Follicular Lymphoma
This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).
- Being tested
- Buparlisib
- Keywords
- Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuparlisibDrug
Also called BKM120
100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days
| Study group | Role | What they receive |
|---|---|---|
| DLBCL Cohort | Experimental | Diffuse large B-cell lymphoma cohort Receives: Drug: Buparlisib |
| MCL Cohort | Experimental | Mantle cell lymphoma cohort Receives: Drug: Buparlisib |
| FL Cohort | Experimental | Follicular lymphoma cohort Receives: Drug: Buparlisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)
Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
Measured: Baseline up to 6 months
Secondary outcomes (5)
Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)
Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.
Measured: Baseline up to approximately 44 months
Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)
Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause
Measured: Baseline up to approximately 18 months
Overall Survival (OS) - Percentage of Participants With OS Events (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit
Measured: Baseline up to approximately 44 months
Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Measured: Baseline up to approximately 18 months
Overall Survival - Median (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Measured: Baseline up approximately 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2012 (estimated)
- Study start28 Feb 2013
- Primary completion21 Jul 2017
- Study completion21 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 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
- NCT01693614
- Sponsor's protocol ID
- CBKM120Z2402
- Other IDs
- 2012-002208-41
- Status last verified
- Aug 2018
- First submitted
- 4 Sep 2012
- Last updated
- 28 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Younes A, Salles G, Martinelli G, Bociek RG, Barrigon DC, Barca EG, Turgut M, Gerecitano J, Kong O, Pisal CB, Tavorath R, Kim WS. Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica. 2017 Dec;102(12):2104-2112. doi: 10.3324/haematol.2017.169656. Epub 2017 Sep 29.
PubMed 28971900
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase II Study of BKM120 in Subjects With Relapsed and Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma and Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT01693614
- Acronym / sponsor ID
- CBKM120Z2402
- Keywords
- Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2013 (actual)
- Primary completion
- 21 Jul 2017 (actual)
- Study completion
- 21 Jul 2017 (actual)
- First posted
- 26 Sep 2012 (estimated)
- Results
- Posted 28 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DLBCL Cohort | Experimental | Drug: BuparlisibDiffuse large B-cell lymphoma cohort |
| MCL Cohort | Experimental | Drug: BuparlisibMantle cell lymphoma cohort |
| FL Cohort | Experimental | Drug: BuparlisibFollicular lymphoma cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma.
- Patient had relapsed or refractory disease and received at least one prior therapy.
- Patient with diffuse large B cell lymphoma had received or was ineligible for autologous or allogeneic stem cell transplant.
- Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the long axis at baseline, then the patient must have had at least one measurable extra-nodal lesion.
- Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Key exclusion criteria (8 listed)
- Patient had received previous treatment with PI3K inhibitors
- Patient had evidence of graft versus host disease (GVHD).
- Patient had active or history of central nervous system (CNS) disease.
- Patient had a concurrent malignancy or had a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer).
- Patient had a score ≥ 12 on the PHQ-9 questionnaire.
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 |
|---|---|---|
| BuparlisibAlso: BKM120100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days | Drug | DLBCL Cohort, FL Cohort, MCL Cohort |
Primary outcome
Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)
Time frame: Baseline up to 6 months
Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
5 secondary outcomes
Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)
Time frame: Baseline up to approximately 44 months
Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)
Time frame: Baseline up to approximately 18 months
Overall Survival (OS) - Percentage of Participants With OS Events (FAS)
Time frame: Baseline up to approximately 44 months
Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)
Time frame: Baseline up to approximately 18 months
Overall Survival - Median (FAS)
Time frame: Baseline up approximately 44 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28971900Younes A, Salles G, Martinelli G, Bociek RG, Barrigon DC, Barca EG, Turgut M, Gerecitano J, Kong O, Pisal CB, Tavorath R, Kim WS. Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica. 2017 Dec;102(12):2104-2112. doi: 10.3324/haematol.2017.169656. Epub 2017 Sep 29.
- Individual participant dataSharing planned: Undecided
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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
20 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buparlisib in people with Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, run by Novartis Pharmaceuticals at 20 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 28 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, France, Belgium, Germany, Italy 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) (time frame: Baseline up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01693614, which also lists 1 linked publication.
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 28 Sep 2018.