Lymphoma, B-Cell, Marginal ZonePhase 2NCT03093831
Phase II Study of Ibrutinib in Patients With Relapsed or Refractory Marginal Zone Lymphoma
A Phase 2 study testing Ibrutinib in people with Lymphoma, B-Cell, Marginal Zone, run by National Cancer Centre, Singapore at 2 sites in Singapore.
Trial summary
The purpose of this study is to assess the efficacy and safety of Ibrutinib in predominantly Asian patients with relapsed or refractory marginal zone lymphoma. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Lymphoma, B-Cell, Marginal Zone
- What is being tested?
- Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesSingapore
- Study dates
- 8 Jul 2016to 17 Jul 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following criteria to be eligible:
- Histologically proven marginal zone lymphoma (splenic, nodal and extra-nodal subtypes included). Patients with clinical and histological evidence of large-cell transformation should be excluded from participating in this study
- Prior treatment with one or more lines rituximab or rituximab-based chemoimmunotherapy with failure to achieve at least a partial response (PR) or documented disease progression
- Age ≥ 21 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least 1 measurable disease site on computed tomography (CT) scan that is at least 1.5cm in the longest dimension. Lesions that are not well visualized by CT may be measured by magnetic resonance imaging (MRI) instead
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- Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [β-hCG]) at Screening. Women of childbearing potential are defined as sexually mature women who have not undergone a hysterectomy or bilateral tubal ligation or bilateral oopphorectomy or who have not been naturally postmenopausal for > 2 years
- Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug. Patient must have an indication for treatment e.g., symptoms from disease, bulky disease (>5cm), threatened end-organ function, or cytopenias requiring transfusion or growth factor support
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
- Adequate hematological and biochemical parameters within 7 days prior to enrollment as defined below:
- Haematological
- Hb ≥8g/dL
- Platelets ≥100,000/mm3 or ≥50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
- Absolute neutrophil count (ANC) ≥1000/mm3 independent of growth factor support
- Biochemical
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN)
- Total bilirubin ≤1.5 x ULN (unless elevated bilirubin is non-hepatic in origin or due to Gilbert's syndrome)
- Serum creatinine ≤2 x ULN or estimate glomerular filtration rate (GFR)(Cockroft Gault) ≥ 40 mL/min/1.73m2
Who cannot join
- Patients who meet any of the following criteria are not eligible
- Prior chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug
- Prior treatment with ibrutinib or other BTK inhibitors or PI3K delta inhibitors
- Concurrent enrolment in another therapeutic investigational clinical treatment study
- Prior allogeneic hematopoietic stem cell transplant. Prior autologous hematopoietic stem cell transplant is allowed
- Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
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- Known central nervous system lymphoma
- History of prior malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon)
- Requires treatment with strong cytochrome P450(CYP)3A4/5 inhibitors
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrythmias, congestive cardiac failure or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) ≥470 msec
- Known history of Human Immunodeficiency Virus (HIV), or active Hepatitis C or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
- Pregnant or lactating women
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites
Singapore General Hospital
Singapore, 169608
National Cancer Centre Singapore
Singapore, 169610
About this study
Official title: A Phase II Investigator Sponsored Multi-Centre Trial of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Patients With Relapsed or Refractory Marginal Zone Lymphoma
The purpose of this study is to assess the efficacy and safety of Ibrutinib in predominantly Asian patients with relapsed or refractory marginal zone lymphoma.
Read the detailed description
Patient sample:
Patients with histologically proven marginal zone lymphoma (splenic, nodal and extra-nodal subtypes included).
Other important requirements for recruitment into the study:
- Prior treatment with one or more lines rituximab or rituximab-based chemoimmunotherapy with failure to achieve at least a partial response (PR) or documented disease progression
- Age ≥ 21 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least 1 measurable disease site on computed tomography (CT) scan that is at least 1.5cm in the longest dimension.
- Patient must have an indication for treatment e.g., symptoms from disease, bulky disease (>5cm), threatened end-organ function, or cytopenias requiring transfusion or growth factor support
Dosage and Dose Regimen:
560mg of Ibrutinib is administered orally once daily. Patients with mild liver impairment (Child's-Pugh A), ibrutinib 140mg (1 x 140mg capsule) will be administered instead. The patient will continue on treatment until one of the following occurs:
- Patient has disease progression (as assessed by the investigator).
- Patient has an intercurrent illness or adverse events that prevents further ibrutinib administration.
- Patient decides to withdraw from the study.
- Investigator considers withdrawal to be in the best interest of the patient.
- Patient requires continuous therapy on a prohibited concomitant medication and no alternative medications or therapies are available as a replacement to the prohibited medication.
- Patient is lost to follow-up.
- Patient is non-compliant.
- Patient becomes pregnant.
- Study termination by the Sponsor or regulatory authority.
- Death
- Completed 3 years of ibrutinib treatment
Assessment:
CT Neck to pelvis or FDG-PET/CT skull base to mid-thigh to be performed repeated after every 12 weeks
Statistical considerations:
The primary objective of this study is to determine the efficacy of ibrutinib in Asian patients with relapsed or refractory MZL. We will consider an ORR of 50% to be desirable. Simon's 2-stage minimax design will be used to test the null hypothesis that the overall response rate will be less than or equal to 20% (response rate that is considered not clinically compelling). Twelve subjects will be included in the first stage, and if there are at least 3 responders, a total of 21 subjects will be enrolled. The treatment will be declared ineffective if there are less than 8 responders in total. This design has 90% power to detect an overall response rate of 50% at a 5% significance level.
Study Endpoints:
Primary:
- Overall response rates (complete remission [CR] + partial remission [PR])
Secondary:
- Survival parameters
- Progression-free survival
- Overall survival
- Safety
- Frequency and severity of adverse events
- Frequency of AE requiring discontinuation of study drug or dose reductions
Total sample size:
The planned sample size is 21 patients enrolled at multiple centres in Singapore and South Korea
- Conditions
- Lymphoma, B-Cell, Marginal Zone
- Being tested
- Ibrutinib
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called PCI-32765, Imbruvica
560mg administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib | Experimental | Not described Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rates
Proportion of patients who achieve either a Complete Response (CR) or Partial Response (PR) as best response
Measured: From time of first study drug administration until best overall response of CR or PR is achieved, up to 3 years
Secondary outcomes (4)
Progression-Free Survival
Measured: From time of first study drug administration until first occurence of disease progression or death from any cause, up to 3 years
Overall Survival
Measured: From time of first study drug administration until death from any cause, up to 3 years
Frequency and severity of adverse events
Measured: From the time the ICF is signed until 30 days after the last dose of the study drug
Frequency of adverse events requiring discontinuation of study drug or dose reductions
Measured: From the time the ICF is signed until 30 days after the last dose of the study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study start8 Jul 2016
- Primary completion17 Jul 2020
- Study completion17 Jul 2020
Why it stopped: Study did not meet the objectives and terminated early on 17 Jul 2020 due to poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma, B-Cell, Marginal ZoneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore General Hospital, Samsung Medical Center
- Responsible party
- Sponsor
- Investigators
- Tiffany PL Tang, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03093831
- Sponsor's protocol ID
- 54179060LYM2009
- Status last verified
- Oct 2023
- First submitted
- 23 Mar 2017
- Last updated
- 11 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Investigator Sponsored Multi-Centre Trial of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Patients With Relapsed or Refractory Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT03093831
- Acronym / sponsor ID
- 54179060LYM2009
- Conditions
- Lymphoma, B-Cell, Marginal Zone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study did not meet the objectives and terminated early on 17 Jul 2020 due to poor recruitment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Collaborators
- Singapore General Hospital, Samsung Medical Center
- Study start
- 8 Jul 2016 (actual)
- Primary completion
- 17 Jul 2020 (actual)
- Study completion
- 17 Jul 2020 (actual)
- First posted
- 28 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy and safety of Ibrutinib in predominantly Asian patients with relapsed or refractory marginal zone lymphoma.
Detailed description
Patient sample:
Patients with histologically proven marginal zone lymphoma (splenic, nodal and extra-nodal subtypes included).
Other important requirements for recruitment into the study:
- Prior treatment with one or more lines rituximab or rituximab-based chemoimmunotherapy with failure to achieve at least a partial response (PR) or documented disease progression
- Age ≥ 21 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least 1 measurable disease site on computed tomography (CT) scan that is at least 1.5cm in the longest dimension.
- Patient must have an indication for treatment e.g., symptoms from disease, bulky disease (>5cm), threatened end-organ function, or cytopenias requiring transfusion or growth factor support
Dosage and Dose Regimen:
560mg of Ibrutinib is administered orally once daily. Patients with mild liver impairment (Child's-Pugh A), ibrutinib 140mg (1 x 140mg capsule) will be administered instead. The patient will continue on treatment until one of the following occurs:
- Patient has disease progression (as assessed by the investigator).
- Patient has an intercurrent illness or adverse events that prevents further ibrutinib administration.
- Patient decides to withdraw from the study.
- Investigator considers withdrawal to be in the best interest of the patient.
- Patient requires continuous therapy on a prohibited concomitant medication and no alternative medications or therapies are available as a replacement to the prohibited medication.
- Patient is lost to follow-up.
- Patient is non-compliant.
- Patient becomes pregnant.
- Study termination by the Sponsor or regulatory authority.
- Death
- Completed 3 years of ibrutinib treatment
Assessment:
CT Neck to pelvis or FDG-PET/CT skull base to mid-thigh to be performed repeated after every 12 weeks
Statistical considerations:
The primary objective of this study is to determine the efficacy of ibrutinib in Asian patients with relapsed or refractory MZL. We will consider an ORR of 50% to be desirable. Simon's 2-stage minimax design will be used to test the null hypothesis that the overall response rate will be less than or equal to 20% (response rate that is considered not clinically compelling). Twelve subjects will be included in the first stage, and if there are at least 3 responders, a total of 21 subjects will be enrolled. The treatment will be declared ineffective if there are less than 8 responders in total. This design has 90% power to detect an overall response rate of 50% at a 5% significance level.
Study Endpoints:
Primary:
- Overall response rates (complete remission [CR] + partial remission [PR])
Secondary:
- Survival parameters
- Progression-free survival
- Overall survival
- Safety
- Frequency and severity of adverse events
- Frequency of AE requiring discontinuation of study drug or dose reductions
Total sample size:
The planned sample size is 21 patients enrolled at multiple centres in Singapore and South Korea
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib | Experimental | Drug: Ibrutinib |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically proven marginal zone lymphoma (splenic, nodal and extra-nodal subtypes included). Patients with clinical and histological evidence of large-cell transformation should be excluded from participating in this study
- Prior treatment with one or more lines rituximab or rituximab-based chemoimmunotherapy with failure to achieve at least a partial response (PR) or documented disease progression
- Age ≥ 21 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least 1 measurable disease site on computed tomography (CT) scan that is at least 1.5cm in the longest dimension. Lesions that are not well visualized by CT may be measured by magnetic resonance imaging (MRI) instead
Key exclusion criteria (19 listed)
- Patients who meet any of the following criteria are not eligible
- Prior chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug
- Prior treatment with ibrutinib or other BTK inhibitors or PI3K delta inhibitors
- Concurrent enrolment in another therapeutic investigational clinical treatment study
- Prior allogeneic hematopoietic stem cell transplant. Prior autologous hematopoietic stem cell transplant is allowed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: PCI-32765, Imbruvica560mg administered orally once daily. | Drug | Ibrutinib |
Primary outcome
Overall Response Rates
Time frame: From time of first study drug administration until best overall response of CR or PR is achieved, up to 3 years
Proportion of patients who achieve either a Complete Response (CR) or Partial Response (PR) as best response
4 secondary outcomes
Progression-Free Survival
Time frame: From time of first study drug administration until first occurence of disease progression or death from any cause, up to 3 years
Overall Survival
Time frame: From time of first study drug administration until death from any cause, up to 3 years
Frequency and severity of adverse events
Time frame: From the time the ICF is signed until 30 days after the last dose of the study drug
Frequency of adverse events requiring discontinuation of study drug or dose reductions
Time frame: From the time the ICF is signed until 30 days after the last dose of the study drug
Results and safety
The study was stopped early (reason given: Study did not meet the objectives and terminated early on 17 Jul 2020 due to poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tiffany PL Tang principal investigator
National Cancer Centre, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib in people with Lymphoma, B-Cell, Marginal Zone, run by National Cancer Centre, Singapore at 2 sites in Singapore.
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 18 inclusion and 19 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: stopped early, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. 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?
The study was stopped early (reason given: Study did not meet the objectives and terminated early on 17 Jul 2020 due to poor recruitment). Results are not available in the source record.
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 Rates (time frame: From time of first study drug administration until best overall response of CR or PR is achieved, up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Oct 2023.