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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02603445
Recruitment Status : Completed
First Posted : November 11, 2015
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 8, 2015
First Posted Date  ICMJE November 11, 2015
Last Update Posted Date February 24, 2020
Actual Study Start Date  ICMJE November 16, 2015
Actual Primary Completion Date July 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
Number of participants with adverse events (AEs) [ Time Frame: 24 months ]
Characterized by Frequency, severity and seriousness of AEs, lab abnormalities and other safety parameters such as electrocardiogram (ECG) changes
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
  • Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15 [ Time Frame: Cycle = 28 days ]
  • Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib) [ Time Frame: 24 Months ]
  • AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [ Time Frame: 24 months ]
  • Objective Response Rate (ORR) [ Time Frame: 24 months ]
  • Best Overall Response (BOR) [ Time Frame: 24 months ]
  • Duration of Response (DOR) [ Time Frame: 24 months ]
  • Complete Response (CR) [ Time Frame: 24 months ]
  • Partial Response (PR) [ Time Frame: 24 months ]
  • Stable disease (SD) [ Time Frame: 24 months ]
  • Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
  • Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
  • Exposure to BCL201 and idelalisib as measured by AUC0-24h at C1D15 [ Time Frame: Cycle = 28 days ]
  • Plasma concentration of BCL201, idelalisib and GS-563117 (metabolite of idelalisib) [ Time Frame: 24 Months ]
  • AUC pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [ Time Frame: 24 months ]
  • Objective Response Rate (ORR) [ Time Frame: 24 months ]
  • Best Overall Response (BOR) [ Time Frame: 24 months ]
  • Duration of Response (DOR) [ Time Frame: 24 months ]
  • Progression free survival (PFS) [ Time Frame: 24 months ]
  • Change from baseline in markers such as protein expression ofBcl -2-family members, phospho-AKT, and Ki67 [ Time Frame: For dose escalation: C1D15, C2D1; For dose expansion: C2D1, C2D15 to C3D1 ]
  • Complete Response (CR) [ Time Frame: 24 months ]
  • Partial Response (PR) [ Time Frame: 24 months ]
  • Stable disease (SD) [ Time Frame: 24 months ]
  • Cmax pharmacokinetics (PK) parameter for BCL201, idelalisib and GS-563117 [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety and Efficacy of BCL201 and Idelalisib in Patients With FL and MCL
Official Title  ICMJE A Phase Ib Dose Escalation Study of BCL201 in Combination With Idelalisib in Patients With Follicular Lymphoma (FL) and Mantle Cell Lymphoma (MCL)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Follicular Lymphoma, Mantle Cell Lymphoma
Intervention  ICMJE
  • Drug: BCL201
    Other Name: S55746
  • Drug: Idelalisib
    Other Name: Idela
Study Arms  ICMJE
  • Experimental: Follicular lymphoma (FL)
    Interventions:
    • Drug: BCL201
    • Drug: Idelalisib
  • Experimental: Mantle cell lymphoma (MCL)
    Interventions:
    • Drug: BCL201
    • Drug: Idelalisib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2015)
65
Actual Study Completion Date  ICMJE July 10, 2018
Actual Primary Completion Date July 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   France,   Germany,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02603445
Other Study ID Numbers  ICMJE CBCL201X2102C
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP