Safety and Efficacy of BKM120 in Relapsed and Refractory NHL

NCT01693614 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CBKM120Z24022012-002208-41
• Study Type: interventional
• Target: 72
• Locations: 8 countries
• Sites: 20

Brief 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).

Conditions

Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma

Keywords

Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline up to 6 months

Secondary Outcomes (5)

• Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)

  Baseline up to approximately 44 months

• Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)

  Baseline up to approximately 18 months

• Overall Survival (OS) - Percentage of Participants With OS Events (FAS)

  Baseline up to approximately 44 months

• Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)

  Baseline up to approximately 18 months

• Overall Survival - Median (FAS)

  Baseline up approximately 44 months

Study Arms (3)

DLBCL Cohort

EXPERIMENTAL

Diffuse large B-cell lymphoma cohort

Drug: Buparlisib

MCL Cohort

EXPERIMENTAL

Mantle cell lymphoma cohort

Drug: Buparlisib

FL Cohort

EXPERIMENTAL

Follicular lymphoma cohort

Drug: Buparlisib

Interventions

Buparlisib DRUG

100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days

Also known as: BKM120

DLBCL Cohort; FL Cohort; MCL Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Nebraska Medical Center Univ Nebraska

Omaha, Nebraska, 68198, United States

Location

Memorial Sloan Kettering Dept of Onc.

New York, New York, 10017, United States

Location

Medical University of South Carolina -Hollings Cancer Center Medical Univ of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Bruges, 8000, Belgium

Location

Novartis Investigative Site

Yvoir, 5530, Belgium

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Rennes, 35019, France

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Gyeonggi-do, Korea, 10408, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Samsun, 55139, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 28971900 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 4, 2012
• First Posted: September 26, 2012
• Study Start: February 28, 2013
• Primary Completion: July 21, 2017
• Study Completion: July 21, 2017
• Last Updated: September 28, 2018
• Results First Posted: September 28, 2018

Record last verified: 2018-08

Locations

DE (2); BE (2); KR (2); TU (2); US (5); IT (2); FR (3); ES (2)