Clinical trial NCT02603445: Study of Safety and Efficacy of BCL201 and Idelalisib in Patients With FL and MCL
Official title: A Phase Ib Dose Escalation Study of BCL201 in Combination With Idelalisib in Patients With Follicular Lymphoma (FL) and Mantle Cell Lymphoma (MCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Follicular Lymphoma, Mantle Cell Lymphoma
Keywords: BCL201
idelalisib
Follicular lymphoma
FL
mantle cell lymphoma
MCL
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-11-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase Ib multi-center, open-label study: escalation part followed by expansion part. The primary purpose of the Phase Ib CBCL201X2102C study is to characterize the safety and tolerability of BCL201 combined with idelalisib in patients with FL and MCL.

Approximately 65 patients are to be enrolled.

The primary endpoint for the Phase Ib is frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as ECG changes. An adaptive Bayesian logistic regression model (BLRM) will guide the dose escalation to determine the MTD/RDE in phase Ib. In addition Bayesian regression models will be used to estimate the dose-exposure relationships for both BCL201 and idelalisib in order to guide the escalation steps. A Bayesian method for the expansion part will be used for the primary activity objective.

The study data will be analyzed and reported based on all patients' data of the escalation and expansion part.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of FL or MCL according to WHO 2008
* Relapsed or refractory with at least one (FL) or two (MCL), but not more than four, prior lines of antineoplastic regimens.
* Either FDG-avid on FDG-PET or measurable disease by CT on cross sectional imaging: \> 1.5 cm for nodal lesion, \> 1.0 cm for extra nodal lesion.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Exclusion Criteria:

* For dose escalation part: Patients with MCL at high risk for tumor lysis syndrome
* Prior treatment with PI3Kδ or Bcl-2 inhibitors.
* Any other malignant disease
* History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis
* Inadequate organ function
* Concomitant treatment with:
* Strong CYP3A4/5 inducers or inhibitors
* Sensitive CYP3A4/5 substrates or CYP3A4/5 substrates with narrow therapeutic index (NTI)
* Sensitive CYP2D6 substrates or CYP2D6 substrates with NTI
* Selected dual substrates of CYP3A4/5 and CYP2C8
* Selected dual substrates of CYP3A4/5 and CYP2D6
* Selected dual substrates of OATP and CYP450
* Selected dual substrates of CYP3A4/5 and P-gp
* NTI P-gp substrates
* QT prolonging drugs with a known risk to induce TdP
* Proton pump inhibitors
* Treatment by warfarin or equivalent vitamin K antagonists.
* Other investigational therapies
* Herbal preparations/ medications
* Grapefruit, Seville oranges or products containing either juice

Other protocol-defined inclusion/exclusion may apply.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: 24 months
Secondary outcomes:
measure: Incidence rate of dose limiting toxicities (DLTs)
timeFrame: 24 months
measure: Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15
timeFrame: Cycle = 28 days
measure: Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib)
timeFrame: 24 Months
measure: AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117
timeFrame: 24 months
measure: Objective Response Rate (ORR)
timeFrame: 24 months
measure: Best Overall Response (BOR)
timeFrame: 24 months
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Complete Response (CR)
timeFrame: 24 months
measure: Partial Response (PR)
timeFrame: 24 months
measure: Stable disease (SD)
timeFrame: 24 months
measure: Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117
timeFrame: 24 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Pierre Benite Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: