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Marginal Zone LymphomaPhase 2NCT03520920

BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL)

A Phase 2 study testing Zanubrutinib and Rituximab in people with Marginal Zone Lymphoma and Follicular Lymphoma, run by BeiGene at 4 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

This was a multicenter, open-label, phase 2 study to evaluate efficacy, safety, and tolerability of BGB-3111 (zanubrutinib) 160 milligrams (mg) twice daily (BID) in combination with rituximab in Chinese participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (non-GCB [non-germinal center… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanubrutinib and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
4 sitesChina
Study dates
4 Jan 2018to 28 Aug 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

  • ≥ Age 18 years at time of signing of informed consent.
  • Measurable disease by computed tomography (CT) or positron emission tomography/CT or magnetic resonance imaging, defined as ≥1 nodal lesion that was >1.5 centimeters (cm) in the longest diameter, or ≥1 extra-nodal lesion (for example, hepatic nodules) that was >1 cm in the longest diameter.
  • Availability of archival or fresh tumor tissue sample from an evaluable core or excisional biopsy.
  • Participants meet the following criteria:
  • Cohort 1: R/R non-GCB DLBCL i. Histologically confirmed non-GCB DLBCL per Hans criteria with non-transformed disease; additional methodologies for confirming non-GCB DLBCL may have been considered in consultation with the medical monitor. ii. Relapsed disease (disease progression after most recent therapy for DLBCL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response [CR] or partial response [PR] to therapy for non-GCB DLBCL or disease progression within 6 months after completion of the most recent therapy for non-GCB DLBCL). iii. Must have received at least one standard anthracycline ± rituximab-based treatment (for example, rituximab plus cyclophosphamide, doxorubicin [or epirubicin, hydroxydaunorubicin, or similar], vincristine, and prednisone) or cyclophosphamide, vincristine, and prednisone +/- rituximab for DLBCL.
  • Cohort 2: R/R FL or R/R MZL i. Histologically confirmed CD20+ FL (Grade 1, 2, or 3a) or MZL. ii. Relapsed disease (disease progression after most recent therapy for FL or MZL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response (CR) or partial response (PR) to most recent therapy for FL or MZL, or disease progression within 6 months after completion of the most recent therapy for FL or MZL).
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  • Laboratory parameters as specified below:
  • Hematologic: Platelet count ≥75 x 10^9/liter (L) independent of growth factor or transfusion within 7 days of study entry; absolute neutrophil count (ANC) ≥1 x 10^9/L independent of growth factor within 7 days of study entry, hemoglobin >8 grams/deciliter within 7 days of study entry.
  • Hepatic: Total bilirubin ≤ 2x upper limit of normal (ULN) unless documented Gilbert's syndrome; aspartate aminotransferase/serum glutamic-oxaloacetic transaminase and alanine transaminase/serum glutamic-pyruvic transaminase ≤3x ULN.
  • Renal: Creatinine clearance ≥30 milliliters/minute (as estimated by the Cockcroft-Gault equation based on ideal body weight or as measured by nuclear medicine scan or 24-hour urine collection).
  • International normalized ratio and activated partial thromboplastin time ≤1.5x ULN. Participants with anti-phospholipid syndrome, acquired von Willebrand disease, factor inhibitors or on vitamin K antagonist may have been enrolled after discussion with the Medical Monitor.
  • Left ventricular ejection fraction ≥50%.
  • Life expectancy ≥6 months.
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  • Female participants of childbearing potential must have practiced highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥90 days after the last dose of zanubrutinib, or 12 months after the last dose of rituximab, whichever is longer.
  • Male participants were eligible if vasectomized or if they agreed to the use of barrier contraception in combination with other methods above during the study treatment period and for ≥90 days after the last dose of zanubrutinib.
  • Able to provide written informed consent and could understand and comply with the requirements of the study.

Who cannot join

  • Known central nervous system lymphoma or leukemia.
  • Histological confirmed gastric mucosa-associated lymphoid tissue type MZL.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • Clinically significant cardiovascular disease.
  • History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
  • History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
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  • Severe or debilitating pulmonary disease.
  • Hypersensitivity reaction to zanubrutinib or rituximab or any of the other ingredients of the study drugs.
  • Prior Bruton tyrosine kinase inhibitor treatment.
  • Required ongoing treatment with a strong cytochrome P450 protein inhibitor or inducer.
  • Vaccination with a live vaccine within 28 days of the first dose of study drug.
  • Hematopoietic stem cell transplantation within 6 months of first dose of study drug.
  • Receipt of the following treatment prior to first dose of study drug:
  • Corticosteroids at doses >20 mg/day prednisone equivalent or steroids given with anti-neoplastic intent within 7 days prior to first dose of study drug.
  • Chemotherapy or radiotherapy within 4 weeks.
  • Monoclonal antibody within 4 weeks.
  • Investigational therapy within 4 weeks.
  • Chinese patent medicine with anti-neoplastic intent within 4 weeks.
  • Not recovered from toxicity of any prior anti-cancer therapy to ≤Grade 1, except for alopecia, ANC, hemoglobin (Hgb), and platelets. For ANC, Hgb and platelets, see inclusion criterion #5.
  • Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.
  • 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, history of bariatric surgery, or partial or complete bowel obstruction.
  • Major surgery within 4 weeks prior to first dose of study treatment.
  • Active fungal, bacterial and/or viral infection requiring systemic therapy.
  • Known infection with human immunodeficiency virus, or serologic status reflecting active hepatitis B or C infection as follows:
  • Presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibody (anti-HBc). Participants with presence of anti-HBc, but absence of HBsAg, were eligible if hepatitis B virus (HBV) DNA was <500 international units (IU)/mL, anti-viral therapy started before the first dose of study treatment, and if they were willing to undergo monthly monitoring for HBV reactivation.
  • Presence of hepatitis C virus (HCV) antibody. Participants with presence of HCV antibody were eligible if HCV RNA was undetectable (<15 IU/mL).
  • Pregnant or lactating women.
  • Underlying medical conditions that, in the investigator's opinion, would have rendered the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
  • Concurrent participation in another therapeutic clinical trial.
  • Note: Other protocol defined Inclusion/Exclusion criteria may have applied.

Trial locations and contacts

4 sites in 1 country.

China4 sites

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 200092

  • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

  • The Affiliated Hospital of Xuzhou Medical University

    Xuzhou, Jiangsu, 221000

Other trials in China

About this study

Official title: A Phase 2 Study to Assess the Safety, Tolerability, and Activity of BGB-3111 in Combination With Rituximab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Non-GCB Subtype) and Relapsed/Refractory Indolent Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)

This was a multicenter, open-label, phase 2 study to evaluate efficacy, safety, and tolerability of BGB-3111 (zanubrutinib) 160 milligrams (mg) twice daily (BID) in combination with rituximab in Chinese participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (non-GCB [non-germinal center B-cell-like] subtype) and R/R indolent lymphoma (follicular lymphoma [FL] and marginal zone lymphoma [MZL]).

Being tested
Zanubrutinib, Rituximab
Medical subject headings
Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • ZanubrutinibDrug

    Also called BGB-3111

    Administered zanubrutinib 160 mg orally (PO) BID continuously

  • RituximabDrug

    Administered rituximab 375 mg/m^2 intravenously on Cycle 1 Days 1, 8, 15, 22, and on Day 1 of Cycles 4, 6, 8, 10. Each cycle was 28 days long.

Study groups in NCT03520920
Study groupRoleWhat they receive
R/R Non-GCB DLBCLExperimentalParticipants with non-GCB DLBCL received zanubrutinib plus rituximab for up to progressive disease or intolerance.
Receives: Drug: Zanubrutinib; Drug: Rituximab
R/R FL or MZLExperimentalParticipants with R/R FL or MZL received zanubrutinib plus rituximab for up to progressive disease or intolerance.
Receives: Drug: Zanubrutinib; Drug: Rituximab

What is being measured

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

  1. Overall Response Rate (ORR) As Measured By The Investigator

    The percentage of participants whose best overall response met partial response (PR) or complete response (CR) criteria among all participants. The 95% confidence interval (CI) was calculated with the Clopper-Pearson method.

    Measured: Up to approximately 2.5 years

Secondary outcomes (10)

  1. Duration Of Response (DOR) As Determined By Investigator

    The DOR was defined as the time from the date that the response criteria were first met to the date that progressive disease (PD) was objectively documented or death, whichever occurred first. Medians were estimated by the Kaplan-Meier method with 95% CIs estimated using the Brookmeyer and Crowley method.

    Measured: Up to approximately 2.5 years

  2. DOR: Event-free Rate

    The DOR was defined as the time from the date that the response criteria were first met to the date that progressive disease (PD) was objectively documented or death, whichever occurred first. The event-free rate was estimated by the Kaplan-Meier method with 95% CIs estimated using Greenwood's formula.

    Measured: Up to approximately 2.5 years

  3. Progression-free Survival (PFS) As Determined By Investigator

    The PFS was defined as time from first dose of study treatment until first documentation of progression, assessed per the Lugano Classification, or death, whichever occurred first. Medians were estimated by the Kaplan-Meier method with 95% CIs estimated using the Brookmeyer and Crowley method.

    Measured: Up to approximately 2.5 years

  4. PFS: Event-free Rate

    The PFS was defined as time from first dose of study treatment until first documentation of progression, assessed per the Lugano Classification, or death, whichever occurred first. The event-free rate was estimated by the Kaplan-Meier method with 95% CIs estimated using Greenwood's formula.

    Measured: Up to approximately 2.5 years

  5. Overall Survival (OS)

    The OS was defined as the time from the date of first dose of study treatment to the date of death due to any cause. Medians were estimated by the Kaplan-Meier method with 95% CIs estimated using the method of Brookmeyer and Crowley.

    Measured: Up to approximately 2.5 years

  6. OS: Survival Rate

    The OS was defined as the time from the date of first dose of study treatment to the date of death due to any cause. Survival rates were estimated by the Kaplan-Meier method with 95% CIs estimated using Greenwood's formula.

    Measured: Up to approximately 2.5 years

  7. Time To Response (TTR) As Determined By The Investigator

    The TTR was defined as the time from the date of the first dose of study treatment to the date of the first qualifying response (partial response or better).

    Measured: Up to approximately 2.5 years

  8. Median TTR

    The TTR was defined as the time from the date of the first dose of study treatment to the date of the first qualifying response (partial response or better).

    Measured: Up to approximately 2.5 years

  9. Complete Response Rate As Determined By The Investigator

    The percentage of participants whose best overall response met complete response or complete metabolic response criteria among all participants are reported. The 95% CI was calculated with Clopper-Pearson method.

    Measured: Up to approximately 2.5 years

  10. Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) And Serious TEAEs

    A treatment-emergent adverse event was defined as an adverse event with an onset or worsening (if present pretreatment) starting on or after the first dose of study drug up to 30 days after discontinuation of zanubrutinib or 90 days after discontinuation of rituximab, whichever occurred later; or initiation of new anticancer therapy if it occurred prior to the other 2 dates. Worsening of a treatment-emergent adverse event to Grade 5 beyond Day 30 after the last dose of zanubrutinib or Day 90 after the last dose rituximab was also considered a treatment-emergent adverse event if the event occurred prior to initiation of new anticancer therapy.

    Measured: Up to approximately 2.5 years

Timeline

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

  1. First posted11 May 2018
  2. Study start4 Jan 2018
  3. Primary completion28 Aug 2020
  4. Study completion28 Aug 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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03520920
Sponsor's protocol ID
BGB-3111-213
Other IDs
CTR20170965
Status last verified
Oct 2024
First submitted
28 Apr 2018
Last updated
26 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Qingyuan Zhang, Rong Tao, Zhenyu Li, et al. Zanubrutinib (BGB-3111) in combination with rituximab in patients with relapsed/refractory Non-Hodgkin Lymphoma [EHA-2188].

  • 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 and Rituximab in people with Marginal Zone Lymphoma and Follicular Lymphoma, run by BeiGene at 4 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 17 inclusion and 30 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 4 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 28 Oct 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 (ORR) As Measured By The Investigator (time frame: Up to approximately 2.5 years). 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 NCT03520920, 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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