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

Primary Purpose

Follicular Lymphoma, Mantle Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BCL201
Idelalisib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma, Mantle Cell Lymphoma focused on measuring BCL201, idelalisib, Follicular lymphoma, FL, mantle cell lymphoma, MCL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Follicular lymphoma (FL)

Mantle cell lymphoma (MCL)

Arm Description

Outcomes

Primary Outcome Measures

Number of participants with adverse events (AEs)
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)
Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15
Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib)
AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117
Objective Response Rate (ORR)
Best Overall Response (BOR)
Duration of Response (DOR)
Complete Response (CR)
Partial Response (PR)
Stable disease (SD)
Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117

Full Information

First Posted
October 8, 2015
Last Updated
February 21, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02603445
Brief Title
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

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
November 16, 2015 (Actual)
Primary Completion Date
July 10, 2018 (Actual)
Study Completion Date
July 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, Mantle Cell Lymphoma
Keywords
BCL201, idelalisib, Follicular lymphoma, FL, mantle cell lymphoma, MCL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Follicular lymphoma (FL)
Arm Type
Experimental
Arm Title
Mantle cell lymphoma (MCL)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BCL201
Other Intervention Name(s)
S55746
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
Idela
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Description
Characterized by Frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as electrocardiogram (ECG) changes
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Incidence rate of dose limiting toxicities (DLTs)
Time Frame
24 months
Title
Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15
Time Frame
Cycle = 28 days
Title
Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib)
Time Frame
24 Months
Title
AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117
Time Frame
24 months
Title
Objective Response Rate (ORR)
Time Frame
24 months
Title
Best Overall Response (BOR)
Time Frame
24 months
Title
Duration of Response (DOR)
Time Frame
24 months
Title
Complete Response (CR)
Time Frame
24 months
Title
Partial Response (PR)
Time Frame
24 months
Title
Stable disease (SD)
Time Frame
24 months
Title
Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Pierre Benite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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

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