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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

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
Germany
State/province [14] 0 0
Ulm
Country [15] 0 0
Italy
State/province [15] 0 0
Milano
Country [16] 0 0
Italy
State/province [16] 0 0
Perugia
Country [17] 0 0
Italy
State/province [17] 0 0
Ravenna
Country [18] 0 0
Italy
State/province [18] 0 0
Roma
Country [19] 0 0
Italy
State/province [19] 0 0
Verona
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
New Zealand
State/province [21] 0 0
Takapuna
Country [22] 0 0
New Zealand
State/province [22] 0 0
Wellington
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Pamplona
Country [26] 0 0
Spain
State/province [26] 0 0
Salamanca
Country [27] 0 0
Spain
State/province [27] 0 0
Santander
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leeds
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
clinicaltrials@beigene.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04277637