Clinical trial NCT02569476: BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies
Official title: A Phase 1b Study to Assess Safety, Tolerability and Antitumor Activity of the Combination of BGB 3111 With Obinutuzumab in Subjects With B-Cell Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Lymphoid Malignancies
Keywords: BGB-3111
Zanubrutinib
Obinutuzumab
Lymphoma
Leukemia
Therapeutic uses
B-cell
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2015-10-06
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in combination with obinutuzumab in participants with B-cell lymphoid malignancies.


Eligibility criteria: Inclusion Criteria:

* Aged ≥18 years, able and willing to provide written informed consent and to comply with the study protocol.
* Laboratory parameters as specified below:

  * Hematologic: Platelet count \>40x10\^9/liter (L) (may be post-transfusion); absolute neutrophil count \>1.0x10\^9/L (growth factor use is allowed to bring pre-treatment neutrophils to \>1.0x10\^9 cells/L if marrow infiltration is involved).
  * Hepatic: Total bilirubin \<3 x upper limit normal (ULN); and aspartate aminotransferase and alanine transaminase ≤3 x ULN.
  * Renal: Creatinine clearance ≥50 milliliters/minute (as estimated by the Cockcroft Gault equation or as measured by nuclear medicine scan or 24-hour urine collection); participants requiring hemodialysis will be excluded.
* Anticipated survival of at least 6 months.
* Eastern Cooperative Oncology Group performance status of 0 to 2.
* Female participants of childbearing potential and non-sterile males must have agreed to practice at least one of the following methods of birth control with partner(s) throughout the study and for ≥3 months after discontinuing zanubrutinib or ≥18 months following obinutuzumab treatment, whichever was longer: total abstinence from sexual intercourse, double barrier contraception, intra uterine device or hormonal contraceptive initiated at least 3 months prior to first administration of study drug.
* Male participants must have not donated sperm from first study drug administration, until 3 months after zanubrutinib discontinuation or 18 months following obinutuzumab treatment, whichever is longer.

Exclusion Criteria:

* Known central nervous system lymphoma or leukemia.
* Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
* Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
* History of significant cardiovascular disease.
* Severe or debilitating pulmonary disease.
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.
* Prior Bruton tyrosine kinase inhibitor treatment.
* Used medications which were strong cytochrome P450 (CYP) 3A inhibitors and strong CYP3A inducers.
* Vaccination with a live vaccine within 28 days of the initiation of treatment.
* Allogeneic stem cell transplantation within 6 months, or had active graft versus host disease requiring ongoing immunosuppression.
* Receipt of the following treatment prior to first administration of zanubrutinib, corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 3 weeks, monoclonal antibody within 4 weeks.
* Participated in any investigational drug study within 28 days of study entry, or not recovered from non-hematologic toxicity of any prior chemotherapy up to ≤ Grade 1 (except for alopecia).
* History of other active malignancies within 2 years of study entry.
* Major surgery in the past 4 weeks.
* Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with human immunodeficiency virus, human T cell lymphotropic virus seropositive status.
* Inability to comply with the study procedures.
* Pregnant or nursing women.
* Any illness or condition that in the opinion of the investigator may have affected the safety of treatment or evaluation of any study's endpoints.

Primary outcomes:
measure: Part 1 : Number Of Participants Experiencing Adverse Events
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1: Number Of Participants With Clinical Laboratory Abnormalities
timeFrame: Day -28 to -1 (predose) through 4 years and 8 months
measure: Part 1: Number Of Deaths
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response
timeFrame: Day 1 (first dose) through 4 years and 8 months
Secondary outcomes:
measure: Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Progression-free Survival (PFS)
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Duration Of Response (DOR)
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Time To Response (TTR)
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Overall Survival (OS)
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1 and Part 2: Hematologic Improvement In Participants With CLL
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Apparent Clearance (CL/F) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1 and Part 2: Steady State AUClast Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1 and Part 2: Steady State Cmax of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 1 and Part 2: Steady State Tmax Of Zanubrutinib
timeFrame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
measure: Part 2: Number Of Participants Experiencing Adverse Events
timeFrame: Day 1 (first dose) through 4 years and 8 months
measure: Part 2: Number Of Participants With Clinical Laboratory Abnormalities
timeFrame: Day -28 to -1 (predose) through 4 years and 8 months
measure: Part 2: Number Of Deaths
timeFrame: Day 1 (first dose) through 4 years and 8 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Fort Myers
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Greenslopes
country: Australia
facility: Brisbane Clinic For Lymphoma
state: Queensland
city: Windsor Gardens
country: Australia
facility: Ashford Cancer Centre Research Northeast
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health the Geelong Hospital
state: Victoria
city: Malvern
country: Australia
facility: St Frances Xavier Cabrini Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tam CS, Quach H, Nicol A, Badoux X, Rose H, Prince HM, Leahy MF, Eek R, Wickham N, Patil SS, Huang J, Prathikanti R, Cohen A, Elstrom R, Reed W, Schneider J, Flinn IW. Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Blood Adv. 2020 Oct 13;4(19):4802-4811. doi: 10.1182/bloodadvances.2020002183.