Chronic Lymphocytic Leukemia Clinical Trial
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
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).
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