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LymphomaPhase 2NCT02301364

Buparlisib (BKM120) In Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Recurrent/Refractory Secondary Central Nervous System Lymphoma (SCNSL)

A Phase 2 study testing Buparlisib (BKM120) in people with Lymphoma and Primary Central Nervous System Lymphoma, run by Memorial Sloan Kettering Cancer Center at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find out what effects, good and/or bad, Buparlisib (also known as BKM120) has on lymphoma and the central nervous system. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Buparlisib (BKM120)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
4 sitesUnited States
Study dates
20 Nov 2014to 11 Oct 2016
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

  • Participants must be able to understand and be willing to sign a written informed consent document.
  • Subjects must be at least 18 years of age on the day of consenting to the study.
  • Histologically documented PCNSL or SCNSL. Patients with SCNSL need to have cytology or tissue biopsy documenting lymphomatous involvement of the CNS
  • Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
  • All patients need to have received at least one prior CNS directed therapy. There is no restriction on the number of recurrences.
  • Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) 21 days prior to study registration. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings consistent with CSF disease 21 days prior to study registration.
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  • Participants must have a Karnofsky performance status (KPS) of ≥ 50.
  • Participants must have adequate bone marrow and organ function shown by:
  • Absolute neutrophil count (ANC) ≥ 1.5x 109/L
  • Platelets ≥ 100 x 109/L and no platelet transfusion within the past 14 days prior to study registration
  • Hemoglobin (Hgb) ≥ 9 g/dL and no red blood cell (RBC) transfusion within the past 14 days prior to study registration
  • International Normalized Ratio (INR) ≤ 1.5
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the ULN.
  • Serum bilirubin ≤ upper limit of normal; or total bilirubin ≤ 2.0x the ULN with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome.
  • Participants must be able to take oral medication.
  • Patients must be able to tolerate MRI scans.
  • Patients must be able to tolerate lumbar puncture and/or Ommaya taps.
  • Participants must have recovered to grade 1 toxicity from prior therapy.
  • Participates must be able to submit 20 unstained slides from the initial tissue diagnosis for confirmation of diagnosis and correlative studies
  • Life expectancy of > 3 months (in the opinion of the investigator) Note: Prior autologous stem cell transplant as well as radiation to the CNS is NOT an exclusion criterion. Prior allogenic stem cell transplant IS an exclusion criterion.

Who cannot join

  • Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded. Patient should have complete resolution of their systemic disease not requiring additional systemic therapy (e.g. maintenance rituximab or decadron).
  • The patient has received prior treatment with a PI3K inhibitor, AKT inhibitor, or mTOR inhibitor (e.g. rapamycin, MK2206, perifosine, etc.).
  • Patient is concurrently using other approved or investigational antineoplastic agents
  • Patient has received chemotherapy or targeted anticancer therapy, monoclonal antibodies ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosourea or mitomycin-C prior to starting the study drug, or the patient has not recovered side the side effects of such therapy
  • Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia)
  • Patient requires more than 8 mg of dexamethasone daily or the equivalent
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  • Patient is taking an enzyme inducing anti-epileptic drug (EIAED), including phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine, rufinamide, and felbamate. Participates must be off of any EIAED for a least two weeks prior to starting the study drug
  • Patient is taking a drug known to be a strong inhibitor or inducers of the isoenzyme CYP3A. Participants must be off a strong CYP3A inhibitors and inducers for at least two weeks prior to starting the study drug.
  • Patient is taking a drug with known risk to promote QT prolongation and Torsade de Pointes Patient is currently using herbal preparations or medications. Participants should stop using herbal medications 7 days prior to the first dose of the study drug.
  • Patient is using warfarin or any other Coumadin-derivative anticoagulant. Patients must be off Coumadin-derivative anticoagulants for at least seven days prior to starting the study drug. Low molecular weight heparin is allowed
  • Patient has a history of allergic reactions to compounds of similar chemical or biological composition to buparlisib
  • Patient has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, chronic liver disease, chronic renal disease, pancreatitis, chronic pulmonary disease, or psychiatric illness or social situations that would limit compliance with the study requirements
  • Patient has acute viral hepatitis or a history of chronic or active HBV or HCV infection
  • Patient has an active concurrent malignancy requiring active therapy.
  • Patient is known to have human immunodeficiency virus (HIV) infection
  • Patient has any severe psychiatric disease that would interfere with participation in the trial as determined by the study investigator
  • Patient has ≥ CTCAE grade 3 anxiety
  • Patient has ≥ CTCAE grade 2 diarrhea Patient has a score ≥12 on the PHQ-9 questionnaire
  • Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9-questionaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9).
  • Patient has a GAD-7 mood scale score ≥15.
  • Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others).
  • Patient has active cardiac disease or cardiac dysfunction including any of the following:
  • Left ventricular ejection fraction (LVEF) ,50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO)
  • QTc>480msec on screening ECG (using the QTcF formula)
  • Angina pectoris that requires the use of anti-anginal medications
  • Ventricular arrhythmias except for benign premature ventricular contractions
  • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
  • Conduction abnormality requiring a pacemaker
  • Valvular disease with documented compromise in cardiac function
  • Symptomatic pericarditis
  • Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall motion abnormalities on assessment of left ventricular ejection fraction function
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • Congenital long QT syndrome
  • Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Patient has impaired gastrointestinal function or gastrointestinal disease affecting absorption of buparlisib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive small bowel resection).
  • Patient has poorly controlled diabetes mellitus with a glycosylated hemoglobin >8% or poorly controlled steroid-induced diabetes mellitus with a glycosylated hemoglobin of >8%.
  • Patient underwent major systemic surgery ≤ 2 weeks prior to starting the trial treatment or who has not recovered from the side effects of such surgery.
  • Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive serum hCG laboratory test of > 5 mIU/mL.
  • Patients who have received allogenic stem cell transplants.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Memoral Sloan Kettering Cancer Center

    Basking Ridge, New Jersey

  • Memorial Sloan Kettering Cancer Center @ Suffolk

    Commack, New York, 11725

  • Memorial Sloan Kettering West Harrison

    Harrison, New York, 10604

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase II Trial Of Buparlisib (BKM120) In Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Recurrent/Refractory Secondary Central Nervous System Lymphoma (SCNSL)

The purpose of this study is to find out what effects, good and/or bad, Buparlisib (also known as BKM120) has on lymphoma and the central nervous system.

Being tested
Buparlisib (BKM120)
Keywords
Buparlisib (BKM120), 14-177
Medical subject headings
Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Buparlisib (BKM120)Drug

    Buparlisib 100 mg once daily.

Study groups in NCT02301364
Study groupRoleWhat they receive
Buparlisib (BKM120)ExperimentalThis is an open-label, phase II trial of the pan-PI3K inhibitor buparlisib (BKM120) for patients with recurrent or refractory primary central nervous lymphoma (PCNSL) and recurrent or refractory secondary central nervous lymphoma (SCNSL).
Receives: Drug: Buparlisib (BKM120)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause. PFS will be based on the investigator's assessment of MRI, CSF studies and clinical presentation.

    Measured: 2 years

Secondary outcomes (3)

  1. Number of Participants With Adverse Events

    Adverse events be summarized based on the Common Toxicity Criteria version 4.0.

    Measured: 2 years

  2. Overall Survival

    Overall survival time is defined as the time from treatment start to the date of death due to any cause.

    Measured: 2 years

  3. Overall Response Rate

    This study will use the Macdonald criteria. Specific lesions must be evaluated serially, and comparative analysis of changes in the area of contrast enhancement, as well as the non-enhancing component, should be performed. Complete Response: Complete disappearance of all measurable and non-measurable disease. No new lesions. Partial Response: Great than or equal to 50% decrease over the baseline in the sum of products of perpendicular diameters of all measurable lesions. no progression of non-measurable disease. No new lesions. Stable/No Response: Does not qualify for CT, PR, or progression. Progressive Disease: 25% increase in the sum of products of all measureable lesions over smallest sum observes (or baseline if no decrease), OR clear clinical worsening of any non-measurable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2014 (estimated)
  2. Study start20 Nov 2014
  3. Primary completion11 Oct 2016
  4. Study completion11 Oct 2016

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02301364
Sponsor's protocol ID
14-177
Status last verified
Feb 2017
First submitted
21 Nov 2014
Last updated
19 Oct 2017

Publications

  • Grommes C, Pentsova E, Schaff LR, Nolan CP, Kaley T, Reiner AS, Panageas KS, Mellinghoff IK. Preclinical and clinical evaluation of Buparlisib (BKM120) in recurrent/refractory Central Nervous System Lymphoma. Leuk Lymphoma. 2023 Sep;64(9):1545-1553. doi: 10.1080/10428194.2023.2223734. Epub 2023 Jun 15.

    PubMed 37317993

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Buparlisib (BKM120) in people with Lymphoma and Primary Central Nervous System Lymphoma, run by Memorial Sloan Kettering Cancer Center at 4 sites in United States.

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 20 inclusion and 40 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 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 19 Oct 2017). 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?

Progression Free Survival (time frame: 2 years). 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 NCT02301364, 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 19 Oct 2017.

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