Chronic Lymphocytic LeukemiaPhase 3NCT02991638
Efficacy and Safety of Ibrutinib in Patients With CLL and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers
A Phase 3 study testing Ibrutinib in people with Chronic Lymphocytic Leukemia and Indolent B-cell Lymphomas, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Efficacy and Safety of ibrutinib in patients with chronic lymphocytic leukemia and other indolent B-cell lymphomas who are chronic hepatitis B virus carriers or occult hepatitis B virus carriers Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Indolent B-cell Lymphomas, Chronic Hepatitis B
- What is being tested?
- Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Nov 2016to Jun 2021
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients between age of 18 - 80 years
- Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab
- Pathologically proven B-cell lymphoproliferative neoplasms including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone B-cell lymphoma, and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma).
- Pathologically proven follicular lymphoma, with relapse or disease progression > 12 months after previous rituximab therapy.
- Chronic HBV carriers (HBsAg+)
- Occult HBV carriers (HBsAg-, anti-HBc+ and HBV DNA-)
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- Haematology values within the following limits:
- Absolute neutrophil count (ANC)1000/mm3 independent of growth factor support
- Platelets 100,000/mm3, or 50,000/mm3 if bone marrow is involved, and independent of transfusion support in either situation
- Biochemical values within the following limits:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
- Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft Gault) ≥ 40 mL/min/1.73m2
- Competent to give an informed consent
Who cannot join
- Concomitant chronic liver diseases not related to HBV
- Known history of drug-induced liver injury, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver and portal hypertension
- Known history of drug induced pneumonitis
- Known history of inflammatory bowel disease
- Woman who are pregnant or breast-feeding
- Patients who do not consent to the use of effective contraception during the study
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- Active infections.
- Evidence of ongoing active HBV hepatitis (ALT and/or AST > 2x upper limit of normal, and detectable HBV DNA)
- Patients known to have histological transformation of CLL to an aggressive lymphoma
- Vaccinated with live, attenuated vaccines within 4 weeks of enrolment
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
King Hei Lu, MMedSc, 852-22554361 ext. 1654, khlu@hku.hk
Zoe Chan, BNs, 852-22551654, zoechan1@hku.hk
About this study
Official title: Efficacy and Safety of Ibrutinib in Patients With Chronic Lymphocytic Leukemia and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers
Efficacy and Safety of ibrutinib in patients with chronic lymphocytic leukemia and other indolent B-cell lymphomas who are chronic hepatitis B virus carriers or occult hepatitis B virus carriers
Read the detailed description
Ibrutinib is a selective oral Burton tyrosine kinase inhibitor. Through interfering with the downstream pathways of B-cell receptor signaling, it inhibits proliferation and induces apoptosis in many B-cell lymphoid malignancies. The clinical benefit of ibrutinib has been demonstrated in patients with relapsed/refractory chronic lymphocytic leukaemia, mantle cell lymphoma, small lymphocytic lymphoma, and other indolent B-cell non-Hodgkin lymphomas.
The pivotal trials of ibrutinib excluded HBsAg+ patients. Therefore, the effects of ibrutinib on HBsAg+ and anti-HBc+ patients remain entirely undefined. In view of the B-cell signaling inhibitory activity of ibrutinib, which might be more potent than rituximab in suppressing B-cells, HBV reactivation in patients exposed previously to HBV infection, including chronic HBV carriers and occult HBV carriers, could be a major clinical problem.
To enable ibrutinib to be prescribed in Asia and other regions of the world where HBV is endemic, evidence-based recommendations on prevention of HBV reactivation in at-risk populations, including chronic HBV carriers (HBsAg+), and occult HBV carriers (HBsAg- but anti-HBc+), are urgently needed.
The following treatment regimens will be adopted. Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily.
Relapsed / refractory mantle cell lymphoma: 560 mg daily. Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily. Treatment is continued until disease progression.
A total of 62 patients will be recruited, including 16 HBsAg+ patients, and 46 occult HBV carriers
Sample size calculation of occult HBV carriers For occult HBV carriers, the sample size is calculated according to the following information, based on our previous observations (as detailed in reference 3). The HBV reactivation rate in HBsAg-, anti-HBc+, anti-HBs+ patients is hypothesized to be 34%, which may increase to 68% in HBsAg-, anti-HBc+, but anti-HBs- patients [3]. Assuming a power of 80% and an alpha-risk of 0.1, together with the ratio of anti-HBs+ : anti-HBs- patients to be 2:1, we expect to recruit 42 HBsAg-, anti-HBc+ patients. With a dropout rate of 10%, the total number of patients to be recruited in this group will be 46.
Sample size calculation of HBsAg+ patients For HBsAg+ patients, the sample size is calculated according to the following information, based on our previous observations (as detailed in reference 3). The ratio of occult carriers (HBsAg-, anti-HBc+) : HBsAg+ patients is about 3: 1.3 Hence, the total number of HBsAg+ to be recruited will be 14 (42 divided by 3). With a drop-out rate of 10%, the total number of patients to be recruited in this group will be 16.
Approximate breakdown of number of patients in each category to be recruited Based on our previous observations on the proportions of low-grade B-cell lymphoid malignancies,8 an approximate breakdown of number of patients is as follows: follicular lymphoma (N=32), chronic lymphocytic leukemia/small lymphocytic lymphoma (N=11), marginal zone B-cell lymphoma (N=11), mantle cell lymphoma (N=5), and Waldenstrom macroglobulinemia (N=5).
- Conditions
- Chronic Lymphocytic Leukemia, Indolent B-cell Lymphomas, Chronic Hepatitis B, Lymphoma, Small Lymphocytic, Mantle-Cell Lymphoma, Waldenstrom's Macroglobulinaemia
- Being tested
- Ibrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Hepatitis B, Chronic, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily Relapsed / refractory mantle cell lymphoma: 560 mg daily Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily Treatment is continued until disease progression
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib | Other | Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily Relapsed / refractory mantle cell lymphoma: 560 mg daily Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily Treatment is continued until disease progression Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
proportion of patients achieving CR or partial remission (PR)
Measured: 2 years
Duration of remission
Measured: two year
Rates of HBV Reactivation while on Ibrutinib therapy
Measured: two year
Adverse events and severe adverse events
Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03
Measured: two year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2016 (estimated)
- Study start1 Nov 2016
- Primary completionDec 2020 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP
- Responsible party
- Principal investigator, Professor Yok-lam Kwong, The University of Hong Kong
- Investigators
- Yok Lam Kwong, MD(HK),, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02991638
- Sponsor's protocol ID
- HKUBTK01
- Status last verified
- Apr 2018
- First submitted
- 2 Dec 2016
- Last updated
- 12 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Ibrutinib in Patients With Chronic Lymphocytic Leukemia and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers
- ClinicalTrials.gov ID
- NCT02991638
- Acronym / sponsor ID
- HKUBTK01
- Conditions
- Chronic Lymphocytic Leukemia, Indolent B-cell Lymphomas, Chronic Hepatitis B, Lymphoma, Small Lymphocytic, Mantle-Cell Lymphoma, Waldenstrom's Macroglobulinaemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Janssen, LP
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 13 Dec 2016 (estimated)
- 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.
Efficacy and Safety of ibrutinib in patients with chronic lymphocytic leukemia and other indolent B-cell lymphomas who are chronic hepatitis B virus carriers or occult hepatitis B virus carriers
Detailed description
Ibrutinib is a selective oral Burton tyrosine kinase inhibitor. Through interfering with the downstream pathways of B-cell receptor signaling, it inhibits proliferation and induces apoptosis in many B-cell lymphoid malignancies. The clinical benefit of ibrutinib has been demonstrated in patients with relapsed/refractory chronic lymphocytic leukaemia, mantle cell lymphoma, small lymphocytic lymphoma, and other indolent B-cell non-Hodgkin lymphomas.
The pivotal trials of ibrutinib excluded HBsAg+ patients. Therefore, the effects of ibrutinib on HBsAg+ and anti-HBc+ patients remain entirely undefined. In view of the B-cell signaling inhibitory activity of ibrutinib, which might be more potent than rituximab in suppressing B-cells, HBV reactivation in patients exposed previously to HBV infection, including chronic HBV carriers and occult HBV carriers, could be a major clinical problem.
To enable ibrutinib to be prescribed in Asia and other regions of the world where HBV is endemic, evidence-based recommendations on prevention of HBV reactivation in at-risk populations, including chronic HBV carriers (HBsAg+), and occult HBV carriers (HBsAg- but anti-HBc+), are urgently needed.
The following treatment regimens will be adopted. Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily.
Relapsed / refractory mantle cell lymphoma: 560 mg daily. Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily. Treatment is continued until disease progression.
A total of 62 patients will be recruited, including 16 HBsAg+ patients, and 46 occult HBV carriers
Sample size calculation of occult HBV carriers For occult HBV carriers, the sample size is calculated according to the following information, based on our previous observations (as detailed in reference 3). The HBV reactivation rate in HBsAg-, anti-HBc+, anti-HBs+ patients is hypothesized to be 34%, which may increase to 68% in HBsAg-, anti-HBc+, but anti-HBs- patients [3]. Assuming a power of 80% and an alpha-risk of 0.1, together with the ratio of anti-HBs+ : anti-HBs- patients to be 2:1, we expect to recruit 42 HBsAg-, anti-HBc+ patients. With a dropout rate of 10%, the total number of patients to be recruited in this group will be 46.
Sample size calculation of HBsAg+ patients For HBsAg+ patients, the sample size is calculated according to the following information, based on our previous observations (as detailed in reference 3). The ratio of occult carriers (HBsAg-, anti-HBc+) : HBsAg+ patients is about 3: 1.3 Hence, the total number of HBsAg+ to be recruited will be 14 (42 divided by 3). With a drop-out rate of 10%, the total number of patients to be recruited in this group will be 16.
Approximate breakdown of number of patients in each category to be recruited Based on our previous observations on the proportions of low-grade B-cell lymphoid malignancies,8 an approximate breakdown of number of patients is as follows: follicular lymphoma (N=32), chronic lymphocytic leukemia/small lymphocytic lymphoma (N=11), marginal zone B-cell lymphoma (N=11), mantle cell lymphoma (N=5), and Waldenstrom macroglobulinemia (N=5).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib | Other | Drug: IbrutinibRelapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily Relapsed / refractory mantle cell lymphoma: 560 mg daily Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily Treatment is continued until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Adult patients between age of 18 - 80 years
- Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab
- Pathologically proven B-cell lymphoproliferative neoplasms including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone B-cell lymphoma, and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma).
- Pathologically proven follicular lymphoma, with relapse or disease progression > 12 months after previous rituximab therapy.
- Chronic HBV carriers (HBsAg+)
Key exclusion criteria (10 listed)
- Concomitant chronic liver diseases not related to HBV
- Known history of drug-induced liver injury, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver and portal hypertension
- Known history of drug induced pneumonitis
- Known history of inflammatory bowel disease
- Woman who are pregnant or breast-feeding
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: ImbruvicaRelapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily Relapsed / refractory mantle cell lymphoma: 560 mg daily Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily Treatment is continued until disease progression | Drug | Ibrutinib |
Primary outcome
Overall response rate (ORR)
Time frame: 2 years
proportion of patients achieving CR or partial remission (PR)
Duration of remission
Time frame: two year
Rates of HBV Reactivation while on Ibrutinib therapy
Time frame: two year
Adverse events and severe adverse events
Time frame: two year
Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2018.
- Individual participant dataSharing planned: Undecided
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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.
Yok Lam Kwong, MD(HK), principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ibrutinib in people with Chronic Lymphocytic Leukemia and Indolent B-cell Lymphomas, run by The University of Hong Kong at 1 site in Hong Kong.
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 10 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: status not confirmed, as of the sponsor's last update on 12 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact King Hei Lu, MMedSc (852-22554361 ext. 1654, khlu@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: 2 years). The study lists 4 primary outcomes in all. 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 12 Apr 2018.