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Diffuse Large B-cell LymphomaPhase 2NCT03145064

Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma

A Phase 2 study testing Zanubrutinib in people with Diffuse Large B-cell Lymphoma, run by BeiGene at 11 sites in China.

Completed

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

Official record
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Trial summary

Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow-up, or study termination from sponsor; treatment (up to 2 years), safety follow-up (30 days); survival follow-up until data cutoff for final analysis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
11 sitesChina
Study dates
30 Jun 2017to 3 Sep 2020
Phase
Phase 2
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

  • Histologically confirmed non-germinal center DLBCL, by immunohistochemistry using the Hans algorithm:
  • Cluster of differentiation 10 (CD10)- and B-cell lymphoma 6 protein (BCL6)-,
  • CD10-, BCL6+, but maximal unique match+
  • Men and women ≥ 18 years of age.
  • Eastern Cooperative Oncology Group performance status of 0-2.
  • Measurable disease was defined as at least 1 lymph node > 1.5 centimeters in longest diameter and measurable in 2 perpendicular dimensions.
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  • All participants must have provided fresh tumor biopsy or recent tumor tissue samples (within 2 years of study entry [informed consent form signed]).
  • Received at least one prior therapy for DLBCL that included anthracycline-based chemotherapy.
  • Participant not eligible for or refused intensive chemotherapy and hematopoietic stem cell transplant.
  • Documented failure to achieve at least partial response with, or documented disease progression after response to, the most recent treatment regimen.
  • Neutrophils ≥ 1 x 10^9/liter (L) independent of growth factor support within 7 days of study entry.
  • Platelets ≥ 75 x 10^9/L, independent of growth factor support or transfusion within 7 days of study entry.
  • Creatinine clearance of ≥ 30 milliliters/minute (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate).
  • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
  • Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome), then up to 5 x ULN allowed.
  • Independent of erythropoietin support or transfusion within 7 days of first dose of study drug.
  • International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN.
  • Participants may be enrolled who relapsed after autologous stem cell transplant if they are at least 6 months after transplant, participants should have had no active infections (that is, fungal or viral).
  • Females of childbearing potential must have agreed to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control were defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive. Males must have undergone sterilization-vasectomy, or utilized a barrier method where the female partner utilized the effective forms of birth control noted above.
  • Life expectancy of > 3 months.
  • Able to provide written informed consent and could understand and comply with the requirements of the study.

Who cannot join

  • Current or history of central nervous system lymphoma.
  • Prior exposure to a BTK inhibitor.
  • Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapies or Chinese anti-cancer herbal therapies within 4 weeks of the start of study drug.
  • Major surgery within 4 weeks of screening.
  • Toxicity of ≥ Grade 2 from prior anti-cancer therapy (except for alopecia, absolute neutrophil count [ANC]) and platelets. For ANC and platelets, please follow inclusion criteria #9 [neutrophils] and #10 [platelets]).
  • History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
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  • Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months of screening. Left ventricular ejection fraction is lower than 50% measured by echocardiography.
  • QTcF (Fridericia's correction) > 450 milliseconds or other significant electrocardiogram abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
  • Known human immunodeficiency virus, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).
  • Pregnant or lactating women.
  • Any life-threatening illness, medical condition or organ system dysfunction, which, in the investigator's opinion, could compromise the participant's safety, or put the study at risk.
  • On medications that were strong cytochrome P450 (CYP), family 3, subfamily A (CYP3A) inhibitors or CYP3A inducers.
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

China11 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200000

  • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 200025

  • The First Affiliated Hospital of Soochow University Branch Shizi

    Suzhou, Jiangsu, 215006

  • Institute of Hematology and Hospital of Blood Disease

    Tianjin, Tianjin Municipality, 300020

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

About this study

Official title: A Phase 2, Single Arm, Multicenter, Open-label Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Subjects With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma

Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow-up, or study termination from sponsor; treatment (up to 2 years), safety follow-up (30 days); survival follow-up until data cutoff for final analysis.

Read the detailed description

This is a single-arm, multicenter, open-label Phase 2 study to evaluate efficacy, safety, tolerability of BGB-3111 (zanubrutinib) in participants with relapsed/refractory non-germinal center B-cell (GCB) type diffuse large B-cell lymphoma (DLBCL).

The study will enroll approximately 40 participants treated with zanubrutinib (160 milligrams [mg]) twice daily (BID). All participants in the study were treated until disease progression, unacceptable toxicity, death, withdrawal of consent, or the study was terminated by the sponsor for final analysis. At the time of final analysis, participants who remained on treatment were considered for participation in the extension study when eligible. A treatment cycle consisted of 28 days.

Being tested
Zanubrutinib
Keywords
Relapsed/refractory non-GCB type
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Recurrence

What participants receive

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

  • ZanubrutinibDrug

    Also called BGB-3111, BRUKINSA

    Administered at a dose of 160 mg BID orally.

Study groups in NCT03145064
Study groupRoleWhat they receive
ZanubrutinibExperimentalParticipants received zanubrutinib BID.
Receives: Drug: Zanubrutinib

What is being measured

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

  1. Overall Response Rate

    Overall response rate was defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) as determined by investigator according to the 2014 modification of the International Working Group (IWG) in Non-Hodgkin's lymphoma (NHL) Criteria.

    Measured: Up to approximately 23 months

Secondary outcomes (4)

  1. Progression-free Survival

    Progression-free survival was defined as the time from first dose of zanubrutinib until first documentation of progression (by IWG on NHL criteria) or death, whichever occurred first.

    Measured: Up to 3 years and 2 months

  2. Duration Of Response

    Duration of response was defined as the time from the date that the response criteria were first met to the date that progressive disease was objectively documented or death, whichever occurred first. Duration of response was summarized for responders (with a best overall response of CR or PR) only.

    Measured: Up to 3 years and 2 months

  3. Time To Response

    Time to response was defined as the time from the first dose of zanubrutinib to the documentation of first response. Time to response was summarized for responders (with a best overall response of CR or PR) only.

    Measured: Up to 3 years and 2 months

  4. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    A treatment-emergent adverse event was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up Visit) or initiation of new anticancer therapy, whichever occurred first.

    Measured: From the time of informed consent to 30 days after the last dose of study drug (approximately Up to 3 years and 2 months)

Timeline

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

  1. First posted9 May 2017
  2. Study start30 Jun 2017
  3. Primary completion24 May 2019
  4. Study completion3 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 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03145064
Sponsor's protocol ID
BGB-3111-207
Other IDs
CTR20170091
Status last verified
Oct 2024
First submitted
5 May 2017
Last updated
26 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Yang H, Xiang B, Song Y, Zhang H, Zhao W, Zou D, Lv F, Bai O, Liu A, Li C, Tan Z, Wang W, Gui H, Novotny W, Huang J, Li Y. Zanubrutinib monotherapy for patients with relapsed or refractory non-germinal center diffuse large B-cell lymphoma: results from a phase II, single-arm, multicenter, study. American Society of Clinical Oncology. 2020

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib in people with Diffuse Large B-cell Lymphoma, run by BeiGene at 11 sites in China.

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 21 inclusion and 15 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 11 sites in China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 8 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?

Overall Response Rate (time frame: Up to approximately 23 months). 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 NCT03145064, 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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