Study of Safety and Efficacy of BCL201 and Idelalisib in Patients With FL and MCL

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02603445

Collaborator

(none)

Enrollment

Locations

Arms

31.8

Actual Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma, Mantle Cell Lymphoma	Drug: BCL201 Drug: Idelalisib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 16, 2015

Actual Primary Completion Date :

Jul 10, 2018

Actual Study Completion Date :

Jul 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Follicular lymphoma (FL)	Drug: BCL201 Other Names: S55746 Drug: Idelalisib Other Names: Idela
Experimental: Mantle cell lymphoma (MCL)	Drug: BCL201 Other Names: S55746 Drug: Idelalisib Other Names: Idela

Arm

Intervention/Treatment

Experimental: Follicular lymphoma (FL)

Drug: BCL201

Other Names:

S55746

Drug: Idelalisib

Other Names:

Idela

Experimental: Mantle cell lymphoma (MCL)

Drug: BCL201

Other Names:

S55746

Drug: Idelalisib

Other Names:

Idela

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [24 months]
Characterized by Frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as electrocardiogram (ECG) changes

Secondary Outcome Measures

Incidence rate of dose limiting toxicities (DLTs) [24 months]
Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15 [Cycle = 28 days]
Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib) [24 Months]
AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [24 months]
Objective Response Rate (ORR) [24 months]
Best Overall Response (BOR) [24 months]
Duration of Response (DOR) [24 months]
Complete Response (CR) [24 months]
Partial Response (PR) [24 months]
Stable disease (SD) [24 months]
Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	New York	New York	United States	10017
2	Novartis Investigative Site	Houston	Texas	United States	77030
3	Novartis Investigative Site	Salzburg		Austria	5020
4	Novartis Investigative Site	Pierre Benite Cedex		France	69495
5	Novartis Investigative Site	Toulouse Cedex 9		France	31059
6	Novartis Investigative Site	Freiburg		Germany	79106
7	Novartis Investigative Site	Mainz		Germany	55131