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

NCT02301364 | Completed Phase 2 Results

• 1 other identifier: 14-177
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Lymphoma; Primary Central Nervous System Lymphoma; Recurrent/Refractory Secondary Central Nervous System Lymphoma

Keywords

Buparlisib (BKM120); 14-177

Outcome Measures

Primary Outcomes (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.

  2 years

Secondary Outcomes (3)

• Number of Participants With Adverse Events

  2 years

• Overall Survival

  2 years

• Overall Response Rate

  2 years

Study Arms (1)

Buparlisib (BKM120)

EXPERIMENTAL

This 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).

Drug: Buparlisib (BKM120)

Interventions

Buparlisib (BKM120) DRUG

Buparlisib 100 mg once daily.

Buparlisib (BKM120)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis: collaborator

Study Sites (4)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 37317993 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Christian Grommes, MD
• Organization: Memorial Sloan Kettering Cancer Center

grommesc@mskcc.org

212-639-4058

Study Officials

• Christian Grommes, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: November 25, 2014
• Study Start: November 20, 2014
• Primary Completion: October 11, 2016
• Study Completion: October 11, 2016
• Last Updated: October 19, 2017
• Results First Posted: October 19, 2017

Record last verified: 2017-02

Locations

US (4)