ClinTrial Refer

Trial Acronym
BGB-11417-101

Registration Number
NCT04277637

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

The purpose of this study is to determine the safety, tolerability; Recommended Phase 2 Dose (RP2D), optimal ramp-up dosing schedule; and to evaluate preliminary activity of BGB-11417 monotherapy.

Each patient eligible to participate in this study must meet all applicable criteria:
 
1. Provision of signed and dated written informed consent prior to any study specific procedures, sampling, or analyses
2. Age 18 years or older
3. Confirmed diagnosis of one of the following:
NHL Cohorts:
a. MZL
i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least two prior therapies
ii. Active disease requiring treatment
b. 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 2 prior systemic therapies
c. 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)
d. 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:
e. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (Hallek et al 2008)
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 of at least one of the following criteria:
(1) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
(2) Massive (ie, ≥ 6.0 cm below left costal margin), or progressive, or symptomatic splenomegaly
(3) Massive nodes (ie, ≥ 10.0 cm in longest diameter), or progressive, or symptomatic lymphadenopathy
(4) Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or lymphocyte doubling time of < 6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30 x 109/L (30,000/μL), lymphocyte doubling time should not be used as a single parameter to define treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (eg, infection, steroid administration) should be excluded
(5) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs
(a) Unintentional weight loss of ≥ 10% within the previous 6 months
(b) Significant fatigue (ie, inability to work or perform usual activities)
(c) Fevers ≥ 100.5oF or 38°C for ≥ 2 weeks without other evidence of infection
(d) Night sweats for ≥ 1 month without evidence of infection
(6) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
4. 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
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
6. Adequate organ function defined as:
a. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L ≤ 7 days before first dose of study drug (without growth factor support). There is an exception for patients with bone marrow involvement in which case ANC must be ≥ 0.75 x 109/L
b. Platelets > 40 x 109/L (> 40,000/mm3) ≤ 7 days before first dose of study drug (without growth factor support or transfusion).
c. Hemoglobin > 80 g/L ≤ 7 days before first dose of study drug (independent of growth factor support or transfusion).
d. Creatinine clearance ≥ 50 mL/min as estimated by one of the following:
i. Cockcroft-Gault equation:
(1) (140 - age) x mass (kg)/72 x creatinine (mg/dL); multiply by 0.85 if female
(2) (140 - age) x mass (kg) x 1.23 if male (or 1.04 if female)/creatinine (μmol/L)
ii. CKD-EPI equation
iii. nuclear medicine scan
iv. 24-hour urine collection
e. Adequate liver function indicated by:
i. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase ≤ 2 x upper limit of normal (ULN)
ii. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase ≤ 2 x ULN
f. Total bilirubin level ≤ 1.5 x ULN (unless documented Gilbert’s syndrome)
7. Adequate pancreatic function indicated by:
a. Serum amylase ≤ 1.5 x ULN
b. Serum lipase ≤ 1.5 x ULN
8. Women of childbearing potential must have a negative serum pregnancy test ≤ 7 days before the first dose of study drug. In addition, they must use a highly effective method of birth control initiated before the first dose of study drug, for the duration of the study treatment period, and for ≥ 90 days after the last dose of study drug. See Appendix 11 for highly effective methods of birth control and the definition of childbearing potential.
9. Nonsterile men must use a highly effective method of birth control for the duration of the study treatment period and for ≥ 90 days after the last dose of study drug. During this same period, they must not donate sperm. See Appendix 11 for highly effective methods of birth control and the definition of sterile.
10. Life expectancy of > 6 months
11. Able to comply with the requirements of the study

Each patient eligible to participate in this study must NOT meet any of the following exclusion criteria:
1. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer
2. Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results
3. Known central nervous system involvement by lymphoma/leukemia
4. Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter’s syndrome
5. Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric cell therapy unless ≥ 6 months after cell infusion
6. Prior allogeneic stem cell transplant
7. Use of the following substances prior to the first dose of study drug:
a. ≤ 28 days before the first dose of study drug:
• Any biologic and/or immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, eg, rituximab, and/or cancer vaccine therapy)
b. ≤ 14 days before the first dose of study drug:
• Systemic chemotherapy or radiation therapy
c. ≤ 7 days before the first dose of study drug:
• Corticosteroid given with antineoplastic intent
8. Active fungal, bacterial, and/or viral infection requiring systemic therapy
Note: oral antibiotics for minor bacterial infections are allowed.
9. Prior therapy ≥ 2 months with or progression on a Bcl-2 inhibitor (eg, venetoclax/ABT-199).
10. Major surgery ≤ 4 weeks before the first dose of study treatment
11. Toxicity from prior anticancer therapy that has not recovered to Grade ≤ 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count, see inclusion criterion 3.e.ii(4))
12. Clinically significant cardiovascular disease including the following:
a. Myocardial infarction ≤ 6 months before screening
b. Unstable angina ≤ 3 months before screening
c. New York Heart Association class III or IV congestive heart failure (see Appendix 3)
d. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
e. Heart rate-corrected QT interval > 480 milliseconds based on Fridericia’s formula
f. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
g. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements, at screening, showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg
13. Known infection with HIV or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:
a. Presence of viral hepatitis B surface antigen (HBsAg) or viral hepatitis B core antibody (HBcAb)
Note: Patients with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable and if they are willing to undergo monitoring for HBV reactivation (see Section 6.12.6).
b. Presence of HCV antibody
Note: Patients with presence of HCV antibody are eligible if HCV RNA is undetectable and if they are willing to undergo monitoring for HCV reactivation (see Section 6.12.6).
14. Pregnant or lactating women
15. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedure, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
16. Inability to comply with study procedures
17. Receiving any treatment with a moderate CYP3A4 inhibitor or strong CYP3A4 inhibitor or inducer ≤ 14 days (or 5 half-lives, whichever is longer) before first dose of BGB-11417 (see Appendix 4)
18. History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study drug
19. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis and acute lung diseases
20. Concurrent treatment for CLL/SLL outside this clinical study (including the screening period)
21. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
22. Ongoing, drug-induced liver injury, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
23. History of hypersensitivity to excipient(s) of the BGB-11417 tablet or, for Parts 3 and 4, the zanubrutinib capsule
24. Requires treatment with warfarin
25. History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
26. Receiving drugs known to prolong the QT/QTc interval (see Appendix 10)
27. Vaccination with a live vaccine ≤ 35 days before first dose of study drug
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
28. [Combination cohorts only] Progressive disease while taking a BTK inhibitor

Trial Location Name

Address

Status

Alfred Health (Haematology)

The Alfred, Commercial Road, Melbourne VIC, Australia

Closed

Primary Contact : John Nguyen, john.nguyen@alfred.org.au , 03 9076 7135

Auckland City Hospital (Haematology)

2 Park Rd, Grafton, Auckland 1023, New Zealand

Closed

Primary Contact : Charlie Stratton, clinicaltrialrefer@tewhatuora.govt.nz , N/A

Concord Repatriation General Hospital (Haematology)

Hospital Rd, Concord NSW 2139, Australia

Closed

Primary Contact : Jennifer Harman, SLHD-ConcordHaematologyClinicalResearch@health.nsw.gov.au , 02 9767 6348

Flinders Medical Centre (Haematology)

Flinders Dr, Bedford Park SA 5042, Australia

Closed

Primary Contact : Bakhtiyor Khalikulov, Bakhtiyor.Khalikulov@sa.gov.au , 08 8204 5453

John Flynn Private Hospital

42 Inland Dr, Tugun QLD 4224, Australia

Closed

Primary Contact : Emily Vasiljevski, VasiljevskiE@ramsayhealth.com.au , 07 5598 9733

North Shore Hospital (Haematology)

North Shore Hospital 124 Shakespeare Road, Takapuna, Auckland, New Zealand

Closed

Primary Contact : Haematology trials coordinator, haematology.research@waitematadhb.govt.nz , N/A

Pindara Private Hospital

Allchurch St, Benowa QLD 4217, Australia

Closed

Primary Contact : Emma Langshaw, LangshawE@ramsayhealth.com.au , 0755889093

Royal Adelaide Hospital (Haematology)

Port Rd, Adelaide SA 5000, Australia

Closed

Primary Contact : Chris Hoare, christine.hoare@sa.gov.au , 08 7074 3290

Wellington Hospital (Haematology)

Wellington Regional Hospital 49 Riddiford Street, Newtown, Wellington, New Zealand

Closed

Primary Contact : Cancer and blood trials coordinator, WBCC-ClinicalTrials@ccdhb.org.nz , N/A

BeiGene

Website URL

Link Name

Link URL

ANZCTR

http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=NCT04277637

Clinicaltrials.gov

https://clinicaltrials.gov/ct2/show/NCT04277637

Secondary IDs
BGB-11417-101

Study Type
Interventional

Intervention Code
Treatment - Drugs

Phase
Phase 1

Minimum Age
18

Maximum Age
100

Date Registered
05/03/2020

Date Closed
N/A

Status
Open

Enrolment Type
By Specialist and/or Surgeon Referral

Mutation Status and Biomarker
Any or not stated

Is it a Cohort Trial?
Yes

Is this a Tele-Trial?
No

Can healthy volunteer participate?
No

Cohort Details

Cohort Name

Description

Status

Experimental: Part 1A (NHL Dose Finding)

BGB-11417 Monotherapy Dose Finding: Cohorts of participants with FL, DLBCL, MZL or transformed NHL, will receive oral BGB-11417-101 until the maximum tolerated and recommended phase 2 dose can be determined.

Closed

Experimental: Part 1B (CLL/SLL Dose Finding)

BGB-11417 Monotherapy Dose Finding: Cohorts of participants with CLL/SLL who have a low TLS risk will receive oral BGB-11417-101 until the maximum tolerated and recommended phase 2 dose can be determined.

Closed

Experimental: Part 1C (CLL/SLL/SL Dose Finding)

Closed

Experimental: Part 1D (R/R MCL Mono Cohort)

BGB-11417 Monotherapy 80mg: Participants with R/R MCL

Closed

Experimental: Part 1E (R/R WM Mono Cohort)

BGB-11417 Monotherapy 640mg: Participants with R/R WM

Closed

Experimental: Part 2A (Aggressive NHL) + Food

BGB-11417 Monotherapy Dose Finding: Cohorts of participants with aggressive NHL + food effect

Closed

Experimental: Part 2B (Aggressive NHL) + Food

BGB-11417 Monotherapy 640mg: Cohorts of participants with indolent NHL + food effect

Closed

Experimental: Part 2C (CLL/SLL)

BGB-11417 Monotherapy Dose Finding: Participants with low and high tumour burden considered.

Closed

Experimental: Part 2E (CLL)

BGB-11417 Monotherapy Dose Finding: Participants with low tumour burden (prior venetoclax)

Closed

Experimental: Part 3A (CLL/SLL Dose Finding)

Combination therapy of BGB-11417 and Zanubrutinib (BGB-3111) Dose Finding: Cohorts of participants with CLL/SLL who have a low/high TLS risk will receive oral BGB-11417-101 until the maximum tolerated and recommended phase 2 dose can be determined.

Closed

Experimental: Part 3B (R/R MCL Dose Finding)

Combination therapy of BGB-11417 and Zanubrutinib (BGB-3111) Dose Finding: Bi-Weekly Ramp-up to target dose 320mg.

Closed

Experimental: Part 4A (RR-CLL/SLL)

Combination therapy of BGB-11417 (320mg) and Zanubrutinib (BGB-3111) participants with RR-CLL/SLL

Closed

Experimental: Part 4B Bi-Weekly (TN-CLL/SLL Combo Cohort)

Combination therapy of BGB-11417 (160mg) and Zanubrutinib (BGB-3111) participants with TN-CLL

Closed

Experimental: Part 4C (RR-MCL)

Combination therapy of BGB-11417 (160mg or 320mg) and Zanubrutinib (BGB-3111) participants with RR-MCL

Closed

Experimental: Part 5B (TN-CLL/SLL Dose finding)

Obinutuzumab + BGB-11417 +/- Zanu - Dose finding: Cohorts of participants with TN-CLL/SLL

Closed

Experimental: Part 6A (TN-CLL/SLL)

BGB-11417 + Obinutuzumab Dose Finding.

Closed

Discipline

Health Condition

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