title: The HELIOS trial protocol: a phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia.
abstract: Ibrutinib is an orally administered, covalent inhibitor of Bruton's tyrosine kinase with activity in B-cell malignancies based on Phase I/II studies. We describe the design and rationale for the Phase III HELIOS trial (trial registration: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745) investigating whether ibrutinib added to bendamustine and rituximab (BR) provides benefits over BR alone in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Eligible patients must have relapsed/refractory disease measurable on CT scan and meet ≥ 1 International Workshop on Chronic Lymphocytic Leukemia criterion for requiring treatment; patients with del(17p) are excluded. All patients receive BR (maximum six cycles) as background therapy and are randomized 1:1 to placebo or ibrutinib 420 mg/day. Treatment with ibrutinib or placebo will start concomitantly with BR and continue until disease progression or unacceptable toxicity. The primary end point is progression-free survival. Secondary end points include safety, objective response rate, overall survival, rate of minimal residual disease-negative remissions, and patient-reported outcomes. Tumor response will be assessed using the International Workshop on Chronic Lymphocytic Leukemia guidelines.
authors.affiliation: Department I of Internal Medicine & Center of Integrated Oncology, University of Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Asher A
authors.initials: AA
authors.lastname: Chanan-Khan
authors.forename: Michelle
authors.initials: M
authors.lastname: Mahler
authors.forename: Mariya
authors.initials: M
authors.lastname: Salman
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Steven
authors.initials: S
authors.lastname: Sun
authors.forename: Sen Hong
authors.initials: SH
authors.lastname: Zhuang
authors.forename: Angela
authors.initials: A
authors.lastname: Howes
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride; D000225:Adenine
keywords: B-cell receptor signaling; Bruton's tyrosine kinase; bendamustine; chronic lymphocytic leukemia; ibrutinib; rituximab; small lymphocytic lymphoma