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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

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.

Condition or disease Intervention/treatment Phase
Mature B-Cell Malignancies Drug: BGB-11417 Drug: Zanubrutinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 418 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies
Actual Study Start Date : March 24, 2020
Estimated Primary Completion Date : August 30, 2023
Estimated Study Completion Date : August 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm

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
Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm

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
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

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
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




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Part 1, Part 3: Maximum RP2D of BGB-11417 [ Time Frame: Day 1 to last dose of study drug, an average of 18 months ]
  6. 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 ]

Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  2. 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 ]
  3. Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  4. 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 ]
  5. Time to Maximum Plasma Concentration (Tmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  6. Apparent Clearance (CL/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  7. Apparent volume of distribution (Vz/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  8. 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 ]
  9. 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 ]
  10. Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  11. Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  12. Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  13. Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  14. Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
  15. Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
  16. Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
  17. Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
  18. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04277637


Contacts
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Contact: BeiGene 1-877-828-5568 clinicaltrials@beigene.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: David Simpson BeiGene
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04277637    
Other Study ID Numbers: BGB-11417-101
First Posted: February 20, 2020    Key Record Dates
Last Update Posted: July 8, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
NHL
BCL2 Inhibitor
CLL
MCL
MZL
SLL
Additional relevant MeSH terms:
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Neoplasms
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action