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Trial record 124 of 350 for:    hepatitis b | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by The University of Hong Kong
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Professor Yok-lam Kwong, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT02991638
First received: December 2, 2016
Last updated: December 8, 2016
Last verified: December 2016
  Purpose
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

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Indolent B-cell Lymphomas
Chronic Hepatitis B
Lymphoma, Small Lymphocytic
Mantle-Cell Lymphoma
Waldenstrom's Macroglobulinaemia
Follicular Lymphoma
Drug: Ibrutinib
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • 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


Estimated Enrollment: 62
Study Start Date: December 2016
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Ibrutinib
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
Drug: Ibrutinib
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
Other Name: Imbruvica

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients between age of 18 - 80 years
  2. Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab
  3. 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).
  4. Pathologically proven follicular lymphoma, with relapse or disease progression > 12 months after previous rituximab therapy.
  5. Chronic HBV carriers (HBsAg+)
  6. Occult HBV carriers (HBsAg-, anti-HBc+ and HBV DNA-)
  7. Haematology values within the following limits:

    1. Absolute neutrophil count (ANC)1000/mm3 independent of growth factor support
    2. Platelets 100,000/mm3, or 50,000/mm3 if bone marrow is involved, and independent of transfusion support in either situation
  8. Biochemical values within the following limits:

    1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN)
    2. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
    3. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft Gault) ≥ 40 mL/min/1.73m2
  9. Competent to give an informed consent

Exclusion Criteria:

  1. Concomitant chronic liver diseases not related to HBV
  2. 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
  3. Known history of drug induced pneumonitis
  4. Known history of inflammatory bowel disease
  5. Woman who are pregnant or breast-feeding
  6. Patients who do not consent to the use of effective contraception during the study
  7. Active infections.
  8. Evidence of ongoing active HBV hepatitis (ALT and/or AST > 2x upper limit of normal, and detectable HBV DNA)
  9. Patients known to have histological transformation of CLL to an aggressive lymphoma
  10. Vaccinated with live, attenuated vaccines within 4 weeks of enrolment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02991638

Contacts
Contact: King Hei Lu, MMedSc 852-22554361 ext 1654 khlu@hku.hk
Contact: Zoe Chan, BNs 852-22551654 zoechan1@hku.hk

Locations
Hong Kong
The University of Hong Kong Recruiting
Queen Mary Hospital, Hong Kong
Contact: King Hei Lu, MMedSc    852-22554361 ext 1654    khlu@hku.hk   
Contact: Zoe Chan, BNs    852-22551654    zoechan1@hku.hk   
Principal Investigator: Yok Lam Kwong, MD(HK)         
Sub-Investigator: Eric Tse, MBBS(HK), PhD(Cantab)         
Sponsors and Collaborators
The University of Hong Kong
Janssen, LP
Investigators
Principal Investigator: Yok Lam Kwong, MD(HK), The University of Hong Kong
  More Information

Responsible Party: Professor Yok-lam Kwong, Chair Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT02991638     History of Changes
Other Study ID Numbers: HKUBTK01
Study First Received: December 2, 2016
Last Updated: December 8, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Leukemia, Lymphocytic, Chronic, B-Cell
Hepatitis, Chronic
Hepatitis B
Lymphoma, B-Cell
Hepatitis B, Chronic
Hepatitis, Viral, Human
Leukemia, B-Cell
Lymphoma
Leukemia
Lymphoma, Follicular
Leukemia, Lymphoid
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Lymphoma, Non-Hodgkin
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on March 24, 2017