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

• ClinicalTrials.gov Identifier: NCT02603445
• Recruitment Status: Completed
• First Posted: November 11, 2015
• Last Update Posted: February 24, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: October 8, 2015
• First Posted Date: November 11, 2015
• Last Update Posted Date: February 24, 2020
• Actual Study Start Date: November 16, 2015
• Actual Primary Completion Date: July 10, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: 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)

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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Follicular Lymphoma, Mantle Cell Lymphoma

Intervention

• Drug: BCL201
  Other Name: S55746
• Drug: Idelalisib
  Other Name: Idela

Study Arms

• Experimental: Follicular lymphoma (FL)
  Interventions:

  • Drug: BCL201
  • Drug: Idelalisib
• Experimental: Mantle cell lymphoma (MCL)
  Interventions:

  • Drug: BCL201
  • Drug: Idelalisib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 19, 2018): 20
• Original Estimated Enrollment (submitted: November 10, 2015): 65
• Actual Study Completion Date: July 10, 2018
• Actual Primary Completion Date: July 10, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02603445
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: February 2020