Chronic lymphocytic leukaemia: Interim analysis data of Phase 3 HELIOS trial announced

Data from a pre-planned interim analysis of the phase 3 CLL3001 (HELIOS) trial show that, at a median follow-up of 17.2 months, the combination of ibrutinib with bendamustine and rituximab (BR) in patients with relapsed / refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) significantly improved progression free survival (PFS) and overall response rate (ORR). The data were assessed by an independent review committee (IRC) and compared to the combination of placebo with BR (HR: 0.203, 95% CI:0.150-0.276, P<0.0001). Median overall survival was not reached in both arms.¹

Janssen announced that the data will be included in the official press programme at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. The data will be presented in full by the lead author of the study, Dr. Asher Chanan-Khan, based at the Mayo Clinic in Jacksonville, Florida, in an oral, late-breaking abstract session during the Leukaemia, Myelodysplasia, and Transplantation track. In addition, the data will be presented as an encore at Europe's most prestigious haematology specialist congress - the European Hematology Association Annual Meeting - taking place on 11-14 June, 2015 in Vienna, Austria.

Following the results of the pre-planned interim analysis, the IRC recommended HELIOS to be unblinded and patients receiving placebo plus BR to be offered to receive ibrutinib.²

"The HELIOS data are particularly exciting, as they demonstrate that ibrutinib combination therapy improved PFS rates three-fold in previously treated patients with CLL or SLL," said Simon Rule, M.D., Consultant Haematologist, Department of Haematology, and Head of the Lymphoma Service, Derriford Hospital, Plymouth, UK, and HELIOS (CLL3001) study investigator.

"As clinicians, we have continued to search for safe and effective options for people who have relapsed or become refractory to treatment. These results suggest the combination of ibrutinib, bendamustine and rituximab is a favourable option for patients who have received previous therapy."

HELIOS is a Janssen-sponsored, randomised, double-blind, placebo-controlled, international, multi-centre Phase 3 study conducted in 21 countries, which evaluated the safety and efficacy of ibrutinib in combination with BR in 578 patients with relapsed or refractory CLL/SLL who had received at least one prior therapy. Patients were randomised to receive either the combination of 420 mg ibrutinib orally once daily and six cycles of BR, or a matching regimen of placebo orally once daily and six cycles of BR, with ibrutinib or placebo continued until disease progression or unacceptable toxicity.¹ The primary endpoint was IRC-assessed PFS and key secondary endpoints included overall survival (OS) and ORR per IRC.

The difference in PFS rates between study arms was consistent across all subgroups. The IRC- assessed ORR and complete response/complete remission (CR/CRi) rates were 82.7 percent and 10.4 percent, respectively, for people taking ibrutinib+BR versus 67.8 percent and 2.8 percent for people in the placebo+BR arm. While the median OS has not yet been reached in either arms, the overall survival results are confounded as 90 patients (31 percent) in the placebo+BR arm with confirmed progressive disease had crossed over to receive ibrutinib. The safety profile of ibrutinib+BR was consistent with the known individual safety profiles for ibrutinib and BR therapies, respectively.¹

Rozlyn Bekker, Medical Director of Janssen, stated: "Janssen is working to bring new therapies to patients living with complex and challenging-to-treat blood cancers. The HELIOS data demonstrate the potential benefits of ibrutinib when combined with standard chemotherapy for people with CLL or SLL, whose disease has progressed, and represent the second Phase 3 trial to demonstrate that ibrutinib significantly delays progression for previously treated patients with these diseases."

The most common all-Grade adverse events (AEs ≥20 percent) in the HELIOS trial were neutropenia (58.2 percent in the ibrutinib+BR arm vs. 54.7 percent in the placebo+BR arm), nausea (36.9 percent vs. 35.2 percent), diarrhoea (35.5 percent vs. 23.7 percent), thrombocytopenia (30.7 percent vs. 24.4 percent), pyrexia (24.7 percent vs. 22 percent), anaemia (22.6 percent vs. 28.9 percent) and fatigue (21.6 percent vs. 22.6 percent). The most common Grade 3/4 AEs (≥15 percent) were neutropenia (53.7 percent vs. 50.5 percent) and thrombocytopenia (15 percent in both arms). Higher rates of Grade 1/2 bleeding such as hematoma (8 percent vs. 1 percent), contusion (7.7 percent vs. 3.1 percent), epistaxis (5.9 percent vs. 3.1 percent), ecchymosis (3.1 percent vs. 0.7 percent) and petechiae (2.8 percent vs. 0.3 percent) were observed in patients taking ibrutinib+BR versus those in the placebo+ BR arm. Rates of major haemorrhage (defined as serious or Grade 3 or greater events) were 3.8 percent (11 cases) and 1.7 percent (5 cases) respectively. Few patients had Grade 3/4 atrial fibrillation (8 cases or 2.8 percent and 2 cases or 0.7 percent), with most patients having a history of prior atrial fibrillation or cardiac risk factors. Overall, 14.2 percent of patients in the ibrutinib arm discontinued due to AEs, as compared to 11.8 percent of patients in the placebo arm.1 There was no difference in second primary malignancies between arms.

For safety information on ibrutinib please go to the following link: https://www.medicines.org.uk/emc/medicine/29383.

A full study report for HELIOS is being prepared and planned to be submitted to health authorities for future labelling considerations. For additional study information: ClinicalTrials.gov.