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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04277637




Registration number
NCT04277637
Ethics application status
Date submitted
18/02/2020
Date registered
20/02/2020
Date last updated
29/10/2024

Titles & IDs
Public title
Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies
Scientific 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
Secondary ID [1] 0 0
BGB-11417-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mature B-Cell Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-11417
Treatment: Drugs - Zanubrutinib
Treatment: Drugs - obinutuzumab

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, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined

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

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; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with 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; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with zanubrutinib

Experimental: : BGB-11417 + Zanubrutinib Combination Therapy Dose Escalation: Part 5 - Participants with treatment naïve CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with obinutuzumab without and with zanubrutinib.

Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 6 - Participants with treatment naïve CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with obinutuzumab without and with zanubrutinib


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

Treatment: Drugs: Zanubrutinib
320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)

Treatment: Drugs: obinutuzumab
Given as an intravenous infusion administered per label.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [2] 0 0
Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [3] 0 0
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of BGB-11417
Timepoint [3] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [4] 0 0
Part 1, Part 3: Maximum Tolerated Dose (MTD)
Timepoint [4] 0 0
Day 1 to 21 days target dose of the study drug, an average of 18 months
Primary outcome [5] 0 0
Part 1, Part 3: Maximum RP2D of BGB-11417
Timepoint [5] 0 0
Day 1 to last dose of study drug, an average of 18 months
Primary outcome [6] 0 0
Part 1, Part 3: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
Timepoint [6] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Secondary outcome [1] 0 0
Maximum Observed Plasma Concentration (Cmax) of BGB-11417
Timepoint [1] 0 0
Predose up to 12 hours postdose
Secondary outcome [2] 0 0
Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417
Timepoint [2] 0 0
Predose up to 12 hours postdose
Secondary outcome [3] 0 0
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-8) of BGB-11417
Timepoint [3] 0 0
Predose up to 12 hours postdose
Secondary outcome [4] 0 0
Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417
Timepoint [4] 0 0
Predose up to 12 hours postdose
Secondary outcome [5] 0 0
Time to Maximum Plasma Concentration (Tmax) of BGB-11417
Timepoint [5] 0 0
Predose up to 12 hours postdose
Secondary outcome [6] 0 0
Apparent Clearance (CL/F) of BGB-11417
Timepoint [6] 0 0
Predose up to 12 hours postdose
Secondary outcome [7] 0 0
Apparent volume of distribution (Vz/F) of BGB-11417
Timepoint [7] 0 0
Predose up to 12 hours postdose
Secondary outcome [8] 0 0
Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of BGB-11417
Timepoint [8] 0 0
Predose up to 12 hours postdose
Secondary outcome [9] 0 0
Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib
Timepoint [9] 0 0
Predose up to 12 hours postdose
Secondary outcome [10] 0 0
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417
Timepoint [10] 0 0
Predose up to 12 hours postdose
Secondary outcome [11] 0 0
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib
Timepoint [11] 0 0
Predose up to 12 hours postdose
Secondary outcome [12] 0 0
Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417
Timepoint [12] 0 0
Predose up to 12 hours postdose
Secondary outcome [13] 0 0
Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib
Timepoint [13] 0 0
Predose up to 12 hours postdose
Secondary outcome [14] 0 0
Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417
Timepoint [14] 0 0
Predose up to 12 hours postdose
Secondary outcome [15] 0 0
Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib
Timepoint [15] 0 0
Predose up to 12 hours postdose
Secondary outcome [16] 0 0
Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed)
Timepoint [16] 0 0
Predose up to 12 hours postdose
Secondary outcome [17] 0 0
Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed)
Timepoint [17] 0 0
Predose up to 12 hours postdose
Secondary outcome [18] 0 0
Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator
Timepoint [18] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months

Eligibility
Key inclusion criteria
Key

* 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 Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy 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:

g. 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)

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

1. 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
2. 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
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Adequate organ function
* Adequate pancreatic function indicated by:

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

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known central nervous system involvement by lymphoma/leukemia
* Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/08/2027
Actual
Sample size
Target
537
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Orange Health Service (Central West Cancer Care Centre) - Orange
Recruitment hospital [3] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [4] 0 0
John Flynn Private Hospital - Tugun
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford PK
Recruitment hospital [7] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
Monash Health - Clayton
Recruitment hospital [9] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [10] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [11] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [12] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
4217 - Benowa
Recruitment postcode(s) [4] 0 0
4224 - Tugun
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Bedford PK
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy
Recruitment postcode(s) [10] 0 0
3000 - Melbourne
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Italy
State/province [14] 0 0
Milano
Country [15] 0 0
Italy
State/province [15] 0 0
Perugia
Country [16] 0 0
Italy
State/province [16] 0 0
Ravenna
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
New Zealand
State/province [18] 0 0
Auckland
Country [19] 0 0
New Zealand
State/province [19] 0 0
Takapuna
Country [20] 0 0
New Zealand
State/province [20] 0 0
Wellington
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Salamanca
Country [24] 0 0
Spain
State/province [24] 0 0
Santander
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
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 and obinutuzumab.
Trial website
https://clinicaltrials.gov/study/NCT04277637
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Simpson
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
1-877-828-5568
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04277637