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Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04277637
Recruitment Status : Recruiting
First Posted : February 20, 2020
Last Update Posted : July 8, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE February 18, 2020
First Posted Date  ICMJE February 20, 2020
Last Update Posted Date July 8, 2022
Actual Study Start Date  ICMJE March 24, 2020
Estimated Primary Completion Date August 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
  • Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
  • Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
  • Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of BGB-11417 [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
  • Part 1, Part 3: Maximum Tolerated Dose (MTD) [ Time Frame: Day 1 to 21 days target dose of the study drug, an average of 18 months ]
  • Part 1, Part 3: Maximum RP2D of BGB-11417 [ Time Frame: Day 1 to last dose of study drug, an average of 18 months ]
  • Part 1, Part 3: Number of participants experiencing tumor lysis syndrome (TLS) relevant events [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Phase 1a: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1a: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1a: Number of participants experiencing AEs leading to discontinuation of BGB-11417 [ Time Frame: Up to 30 days after the last dose of study drug ]
  • 7. Phase 1a: Maximum Tolerated Dose (MTD) as Assessed by the Safety Monitoring Committee (SMC) [ Time Frame: Day 1 to 21 days target dose of the study drug ]
  • Phase 1a: Maximum RP2D of BGB-11417 [ Time Frame: Day 1 to last dose of study drug ]
  • Phase 1b: Optimal ramp-up schedule of BGB-11417 [ Time Frame: Up to 30 days after the last dose of study drug ]
    A ramp-up schedule is defined as the BGB-11417 dosing schedule a participant utilizes to gradually reach or "ramp-up" to the intended target dose and schedule
  • Phase 1b: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Number of participants experiencing AEs leading to discontinuation of BGB-11417 [ Time Frame: Up to 30 days after the last dose of study drug ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • Maximum Observed Plasma Concentration (Cmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Time to Maximum Plasma Concentration (Tmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Apparent Clearance (CL/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Apparent volume of distribution (Vz/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  • Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  • Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  • Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  • Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
  • Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
  • Part 2, Part 4: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
    ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug ]
    ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
  • Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • : Phase 1a: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Apparent Clearance (CL/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Apparent volume of distribution (Vz/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last Day (AUCLast, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a; Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1a: Observed accumulation ratio based on Area under the curve (AUCRo) Cmax of BGB-11417 [ Time Frame: Predose up to 12 hours postdose following repeated dosing at each targeted dose levels ]
  • Phase 1a: Observed accumulation ratio based on Cmax (RCmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose following repeated dosing at each targeted dose levels ]
  • Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug ]
    ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
  • Phase 1b: Progression-Free Survival (PFS) [ Time Frame: Time from start of treatment to the first documentation of disease progression or death, whichever occurs first ]
  • Phase 1b: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Time from first determination of response until first documentation of progression or death ]
  • Phase 1b: Time to Response (TTR) as Assessed by the Investigator [ Time Frame: Time from start of treatment to first documentation of response ]
  • Phase 1b: Overall survival (OS) as Assessed by the Investigator [ Time Frame: Time from start of treatment to the date of death due to any cause ]
  • Phase 1b: Rate of Minimal Residual Disease (MRD) negativity in Blood [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Rate of Minimal Residual Disease (MRD) negativity in Bone Marrow [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Maximum Observed Plasma Concentration (Cmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Time to Maximum Plasma Concentration (Tmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Apparent Clearance (CL/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b Apparent volume of distribution (Vz/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Steady State Area Under the Concentration-Time Curve of 0- Last Day (AUCLast, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417 [ Time Frame: Predose up to 112 hours postdose ]
  • Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  • : Phase 1b; Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-324511417 [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b; Change in AUC of BGB-3245 11417 from Fasted to Fed Condition [ Time Frame: Predose up to 12 hours postdose ]
  • Phase 1b; Change in Cmax of BGB-11417 from Fasted to Fed Condition [ Time Frame: Predose up to 12 hours postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies
Official Title  ICMJE A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies
Brief Summary The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mature B-Cell Malignancies
Intervention  ICMJE
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
  • Drug: Zanubrutinib
    320 mg administered as twice-daily zanubrutinib should be administered as two 80-mg capsules twice a day (160 mg twice a day) or oOnce-daily zanubrutinib should be administered as four 80-mg capsules once a day (320 mg once a day)
    Other Name: BGB-3111
Study Arms  ICMJE
  • Experimental: BGB-11417 Monotherapy Dose Finding: Part 1
    Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL; chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined
    Intervention: Drug: BGB-11417
  • Experimental: BGB-11417 Monotherapy Expansion Cohorts: Part 2
    Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile
    Intervention: Drug: BGB-11417
  • Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Finding: Part 3
    Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 until RP2D can be determined in combination with zanubrutinib
    Interventions:
    • Drug: BGB-11417
    • Drug: Zanubrutinib
  • Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 4
    Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile in combination with zanubrutinib
    Interventions:
    • Drug: BGB-11417
    • Drug: Zanubrutinib
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2021)
418
Original Estimated Enrollment  ICMJE
 (submitted: February 18, 2020)
160
Estimated Study Completion Date  ICMJE August 30, 2023
Estimated Primary Completion Date August 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

1.

Confirmed diagnosis of one of the following:

NHL Cohorts:

  1. MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment
  2. FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
  3. DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy)
  4. Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1.

    CLL/SLL Cohorts:

  5. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as R/R disease defined as disease that relapsed after, or was refractory to, at least 2 prior therapies ii. Requiring treatment as defined by history

    MCL cohorts:

  6. WHO-defined MCL I. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigatorr

    WM cohorts:

  7. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014) 2.

Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as:

a. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry b. DLBCL, FL, MZL, SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 4. Adequate organ function 5.

Adequate pancreatic function indicated by:

  1. Serum amylase ≤ 1.5 x upper limit of normal (ULN)
  2. Serum lipase ≤ 1.5 x ULN

Key Exclusion Criteria:

  1. Known central nervous system involvement by lymphoma/leukemia
  2. Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
  3. Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor

NOTE: Other protocol defined Inclusion/Exclusion criteria 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: BeiGene 1-877-828-5568 clinicaltrials@beigene.com
Listed Location Countries  ICMJE Australia,   New Zealand,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04277637
Other Study ID Numbers  ICMJE BGB-11417-101
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: Yes
Current Responsible Party BeiGene
Original Responsible Party Same as current
Current Study Sponsor  ICMJE BeiGene
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Simpson BeiGene
PRS Account BeiGene
Verification Date July 2022

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