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B-cell Lymphoid MalignanciesPhase 1NCT02569476

BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies

A Phase 1 study testing Zanubrutinib and Obinutuzumab in people with B-cell Lymphoid Malignancies, run by BeiGene at 14 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in combination with obinutuzumab in participants with B-cell lymphoid malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-cell Lymphoid Malignancies
What is being tested?
Zanubrutinib and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
14 sitesin 3 countries
Study dates
13 Jan 2016to 2 Sep 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

Australia8 sites

  • St Vincents Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Barwon Health the Geelong Hospital

    Geelong, Victoria, 3220

  • Brisbane Clinic For Lymphoma

    Greenslopes, Queensland, 4120

  • St George Hospital

    Kogarah, New South Wales, 2217

  • St Frances Xavier Cabrini Hospital

    Malvern, Victoria, 3144

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Ashford Cancer Centre Research Northeast

    Windsor Gardens, South Australia, 5087

Other trials in Australia

United States3 sites

  • Florida Cancer Specialists Fort Myers

    Fort Myers, Florida, 33916

  • Tennessee Oncology

    Nashville, Tennessee, 37205

  • Florida Cancer Specialists East

    West Palm Beach, Florida, 33401

Other trials in United States

South Korea3 sites

  • Asan Medical Center

    Seoul, Seoul Teugbyeolsi, 05505

  • Gangnam Severance Hospital, Yonsei University Health System

    Seoul, Seoul Teugbyeolsi, 06273

  • Samsung Medical Center

    Seoul, Seoul Teugbyeolsi, 06351

Other trials in South Korea

About this study

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

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

Being tested
Zanubrutinib, Obinutuzumab
Keywords
BGB-3111, Zanubrutinib, Obinutuzumab, Lymphoma, Leukemia, Therapeutic uses, B-cell
Medical subject headings
Lymphoma, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02569476
Study groupRoleWhat they receive
Zanubrutinib and ObinutuzumabExperimentalIn the dose-escalation part, dose levels and regimens were evaluated. In the indication-specific expansion cohorts, participants were assigned to different cohorts based on histology type.
Receives: Drug: Zanubrutinib; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 : Number Of Participants Experiencing Adverse Events

    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A serious AE (SAE) was any untoward medical occurrence that, at any dose.

    • resulted in death,
    • was life threatening,
    • required hospitalization or prolongation of existing hospitalization,
    • resulted in disability/incapacity,
    • was a congenital anomaly/birth defect.

    Measured: Day 1 (first dose) through 4 years and 8 months

  2. Part 1: Number Of Participants With Clinical Laboratory Abnormalities

    Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.

    Measured: Day -28 to -1 (predose) through 4 years and 8 months

  3. Part 1: Number Of Deaths

    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose:

    • resulted in death,
    • was life threatening,
    • required hospitalization or prolongation of existing hospitalization,
    • resulted in disability/incapacity,
    • was a congenital anomaly/birth defect.

    Measured: Day 1 (first dose) through 4 years and 8 months

  4. Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)

    Dose-limiting toxicities were defined as a toxicity or AE occurring during the DLT assessment period (first 29 days of treatment), which is not clearly attributable to a cause other than zanubrutinib and/or obinutuzumab (such as disease progression, underlying illness, concurrent illness or concomitant medication) and meets one of the following criteria:

    • Grade 3 or 4 drug-related non-hematologic toxicity (excluding Grade 3 nausea, vomiting, hypertension, and asymptomatic laboratory abnormalities),
    • Grade 4 drug-related hematologic toxicity persisting for >14 days,
    • any grade toxicity, which in the judgment of the investigator or Sponsor, required removal of the participant from the study.

    Measured: Day 1 (first dose) through 4 years and 8 months

  5. Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response

    Partial response was defined as follows:

    • ≥ 50% reduction of serum IgM from baseline,
    • reduction in lymphadenopathy/splenomegaly (if present at baseline). For response assessments that occurred during cycles where a CT scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.

    Measured: Day 1 (first dose) through 4 years and 8 months

Secondary outcomes (19)

  1. Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response

    Complete response was defined as follows:

    • normal serum IgM values,
    • disappearance of monoclonal protein by immunofixation,
    • no histological evidence of bone marrow involvement,
    • complete resolution of lymphadenopathy/splenomegaly (if present at baseline) For response assessments that occurred during cycles where a computed tomography (CT) scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.

    Measured: Day 1 (first dose) through 4 years and 8 months

  2. Part 1 and Part 2: Progression-free Survival (PFS)

    Progression-free survival was defined as time (in months) from the start of treatment with zanubrutinib or obinutuzumab to the first documented disease progression or death due to any cause, whichever occurred first. Results are reported as the median months for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL).

    Measured: Day 1 (first dose) through 4 years and 8 months

  3. Part 1 and Part 2: Duration Of Response (DOR)

    Duration of response for responders was defined as the time (in months) from the date of the earliest qualifying response to the date of progressive disease or death due to any cause (whichever occurred earlier). Duration of response was analyzed using the same methods as the analysis for PFS. Responses after initiating new anticancer therapy, roll over to the long-term extension (LTE) study, or the first occurrence of disease progression were not considered in the analysis.

    Measured: Day 1 (first dose) through 4 years and 8 months

  4. Part 1 and Part 2: Time To Response (TTR)

    The TTR for responders was defined as time (in months) from the start of the study treatment to the date of the earliest qualifying response. The TTR was summarized using descriptive statistics. Responses after initiating new anticancer therapy, roll over to the LTE study, or the first occurrence of disease progression were not considered in the analysis of TTR.

    Measured: Day 1 (first dose) through 4 years and 8 months

  5. Part 1 and Part 2: Overall Survival (OS)

    Overall survival was defined as the time (in months) from the date of the start of the study treatment to death due to any cause. Participants who were alive before final database lock or discontinuation of the study (discontinued study due to reasons other than death) were censored at their last known alive date on or before database lock.

    Measured: Day 1 (first dose) through 4 years and 8 months

  6. Part 1 and Part 2: Hematologic Improvement In Participants With CLL

    The number and percentage of participants with CLL with anemia (hemoglobin ≤110 grams/liter [g/L]), neutropenia (absolute neutrophil count ≤1.5 x 10^9/L), or thrombocytopenia (platelet count ≤100 x 10^9/L) at baseline were estimated.

    Measured: Day 1 (first dose) through 4 years and 8 months

  7. Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  8. Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  9. Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  10. Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  11. Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  12. Part 1: Apparent Clearance (CL/F) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  13. Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  14. Part 1 and Part 2: Steady State AUClast Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  15. Part 1 and Part 2: Steady State Cmax of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  16. Part 1 and Part 2: Steady State Tmax Of Zanubrutinib

    Measured: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7

  17. Part 2: Number Of Participants Experiencing Adverse Events

    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,:

    • resulted in death,
    • was life threatening,
    • required hospitalization or prolongation of existing hospitalization,
    • resulted in disability/incapacity,
    • was a congenital anomaly/birth defect.

    Measured: Day 1 (first dose) through 4 years and 8 months

  18. Part 2: Number Of Participants With Clinical Laboratory Abnormalities

    Results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.

    Measured: Day -28 to -1 (predose) through 4 years and 8 months

  19. Part 2: Number Of Deaths

    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,:

    • resulted in death,
    • is life threatening,
    • required hospitalization or prolongation of existing hospitalization,
    • resulted in disability/incapacity,
    • was a congenital anomaly/birth defect.

    Measured: Day 1 (first dose) through 4 years and 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2015 (estimated)
  2. Study start13 Jan 2016
  3. Primary completion2 Sep 2020
  4. Study completion2 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02569476
Sponsor's protocol ID
BGB-3111_GA101_Study_001
Status last verified
Oct 2024
First submitted
18 Sep 2015
Last updated
26 Oct 2024
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • Liu Y, Ma X, Wu X, Hou X, Jin W, Fu L, Xun X, Yu Y, Shen Z. Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated CD79B, high TCL1A expression, or over- expressed MYC/BCL-2. Leuk Lymphoma. 2024 Aug;65(8):1079-1089. doi: 10.1080/10428194.2024.2343779. Epub 2024 May 22.

    PubMed 38775302

  • 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.

    PubMed 33022066

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Zanubrutinib and Obinutuzumab in people with B-cell Lymphoid Malignancies, run by BeiGene at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Australia, United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 : Number Of Participants Experiencing Adverse Events (time frame: Day 1 (first dose) through 4 years and 8 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02569476, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.

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