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Relapsed or Refractory Chronic Lymphocytic LeukemiaPhase 2NCT03206918

Efficacy and Safety of Zanubrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 2 study testing Zanubrutinib in people with Relapsed or Refractory Chronic Lymphocytic Leukemia and Relapsed or Refractory Small Lymphocytic 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
Search all trials

Trial summary

This was a single-arm, open-label, multi-center Phase 2 study in participants with histologically documented CLL/SLL who have relapsed after or refractory to ≥ 1 prior treatment regimen(s). The study is composed of an initial screening phase, a single-arm treatment phase, and a follow-up phase. Read more about this study

Who is it for?
Ages 18 years and older
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
91 participants
Where
11 sitesChina
Study dates
9 Mar 2017to 10 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

  • Confirmed diagnosis with at least one criterion for treatment according to International workshop on chronic lymphocytic leukemia (IWCLL)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Measurable disease by contrast enhanced computerized tomography / magnetic resonance imaging (CT/MRI).
  • Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥2 treatment cycles).
  • Documented failure to achieve at least partial response (PR) or documented disease progression after response to the most recent treatment regimen. Refractory disease is defined as treatment failure (stable disease, non-response, progressive disease [PD]) or disease progression within 6 months after the most recent prior therapy (Hallek et al, 2008).
  • Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry
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  • Platelets ≥ 50 x 109/L, independent of growth factor support or transfusion within 7 days of study entry
  • Creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate [eGFR] from the Modification of Diet in Renal Disease [MDRD])
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN
  • Bilirubin ≤2 x ULN (unless documented Gilbert's syndrome)
  • International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.
  • Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 6 months after transplant.
  • Life expectancy of >4 months
  • Echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥50%; (AHA, 2016)

Who cannot join

  • Current or history of central nervous system (CNS) lymphoma
  • Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor
  • Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days.
  • Major surgery within 4 weeks of screening
  • Not recovered from toxicity of any prior anti-cancer therapy to <Grade 1 (except for alopecia, absolute neutrophil count (ANC) and 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
  • QTcF >480 msecs based on Fridericia's formula 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
  • Active infection including infections requiring oral or intravenous anti-microbials
  • Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction [PCR]).
  • Has received allogenic hematopoietic stem cell transplantation prior to enrollment
  • Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participants's safety, or put the study at risk
  • Requires ongoing treatment with any medication which is a strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitor or strong CYP3A inducer
  • Known or clinically suspected Richter's transformation at the time of study entry
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • 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

  • Peking University Peoples Hospital

    Beijing, Beijing Municipality, 100044

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510515

  • Jiangsu Province Hospital

    Nanjing, Jiangsu, 210029

  • The First Affiliated Hospital of Soochow University

    Suzhou, Jiangsu, 215006

  • Institute of Hematology and Hospital of Blood Disease

    Tianjin, Tianjin Municipality, 300020

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

    Wuhan, Hubei, 430030

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

About this study

Official title: A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Safety and Efficacy of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

This was a single-arm, open-label, multi-center Phase 2 study in participants with histologically documented CLL/SLL who have relapsed after or refractory to ≥ 1 prior treatment regimen(s). The study is composed of an initial screening phase, a single-arm treatment phase, and a follow-up phase.

Being tested
Zanubrutinib
Keywords
Bruton's tyrosine kinase, Chronic lymphocytic leukemia, Relapsed/refractory, Zanubrutinib
Medical subject headings
Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • ZanubrutinibDrug

    Also called BGB-3111

    Zanubrutinib 160 mg (two - 80 mg white opaque capsules) taken by mouth (PO) twice a day (BID)

Study groups in NCT03206918
Study groupRoleWhat they receive
ZanubrutinibExperimentalNot described
Receives: Drug: Zanubrutinib

What is being measured

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

  1. Overall Response Rate (ORR) by Independent Review Committee (IRC)

    ORR is defined as the number of participants who achieve a best response of CR or, CRi, Nodular Partial Response, PR, and PR with Lymphocytosis as assessed by IRC per the modified IWCLL Guidelines in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.

    Measured: Up to 1 year and 4 months

Secondary outcomes (5)

  1. Progression-free Survival (PFS): Percentage of Participants Progression/Death Event Free

    PFS is defined as the time from treatment initiation to first documentation of progression by International workshop on chronic lymphocytic leukemia (IWCLL) criteria/revised criteria for response for malignant lymphoma or death, whichever is earlier.

    Measured: 6, 12, 24, and 36 months

  2. Duration of Response (DOR): Event Free Rate - Percentage of Participants Who Remained Event Free

    DOR is defined as the time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first

    Measured: 6, 12, 24, and 36 months

  3. Time to Response (TTR)

    TTR is defined as the time from treatment initiation to first signs of response

    Measured: Up to 3.5 years

  4. Overall Response Rate as Determined by the Investigator

    Overall response was defined as achieving a best overall response of CR, CRi, nodular partial response (nPR), PR, or partial response with lymphocytosis (PR-L).

    Measured: up to 3.5 years

  5. Number of Participants Experiencing Adverse Events (AEs)

    An adverse event (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. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version [v] 4.03 2010). A treatment emergent adverse event (TEAE) is defined as an adverse event that has 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 or initiation of new anticancer therapy, whichever occurs first.

    Measured: Up to 3.5 years

Timeline

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

  1. First posted2 Jul 2017
  2. Study start9 Mar 2017
  3. Primary completion15 Jun 2018
  4. Study completion10 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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03206918
Sponsor's protocol ID
BGB-3111-205
Other IDs
CTR20160890
Status last verified
Oct 2024
First submitted
29 Jun 2017
Last updated
26 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Xu W, Yang S, Zhou K, Pan L, Li Z, Zhou J, Gao S, Zhou D, Hu J, Feng R, Huang H, Ji M, Guo H, Huang J, Novotny W, Feng S, Li J. Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study. J Hematol Oncol. 2020 May 11;13(1):48. doi: 10.1186/s13045-020-00884-4.

    PubMed 32393328

  • Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.

    PubMed 38502198

  • Xu W, Yang S, Zhou K, Pan L, Li Z, Gao S, Zhou D, Hu J, Feng R, Huang H, Wang T, Li D, Ji M, Guo H, Zhao X, Wu B, Yu Y, Wang Y, Huang J, Novotny W, Li J. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023 Mar;64(3):712-716. doi: 10.1080/10428194.2022.2164692. Epub 2023 Feb 17. No abstract available.

    PubMed 36799536

  • Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.

    PubMed 35900694

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib in people with Relapsed or Refractory Chronic Lymphocytic Leukemia and Relapsed or Refractory Small Lymphocytic 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 14 inclusion and 17 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 25 Sep 2020). 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) by Independent Review Committee (IRC) (time frame: Up to 1 year and 4 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 NCT03206918, which also lists 4 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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