Phase 3
Completed N=578
A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Source: ClinicalTrials.gov NCT01611090 ↗Enrolled (actual)
578
Serious AEs
56.8%
Results posted
Mar 2020
Primary outcomePrimary: Progression-free Survival (PFS) — 65.12; 14.32 Months — p=< 0.0001
◆ Published Evidence
Highly cited
410citations · ~41 / year
Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.
Summary
The purpose of this study is to examine the safety and efficacy of Ibrutinib administered in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Linked Publications (5)
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Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.
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Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.
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Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.
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Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial.
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Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) |
65.12; 14.32 | < 0.0001 sig |
| SECONDARY Overall Response Rate (ORR) |
87.2; 66.1 | — |
| SECONDARY Overall Survival (OS) |
NA; NA | — |
| SECONDARY Percentage of Participants With Minimal Residual Disease (MRD)-Negative Response |
28.7; 5.9 | — |
| SECONDARY Percentage of Participants With Sustained Hematologic Improvement |
36.7; 29.1; 30.8; 21.8 | — |
| SECONDARY Median Time to Clinically Meaningful Improvement in FACIT-Fatigue Scale |
6.5; 4.6 | — |
| SECONDARY Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms |
0; 0 | — |
| SECONDARY Number of Participants Who Received Subsequent Antineoplastic Therapy |
52; 61 | — |
| SECONDARY Change From Baseline in Beta2 Microglobulin at End of Treatment (EOT) |
-0.46; -0.23 | — |
| SECONDARY Change From Baseline in FACIT-Fatigue Scale at End of Treatment |
-0.9; 0.0 | — |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Physical Functioning Score at End of Treatment |
-2.1; -4.1 | — |
| SECONDARY Change From Baseline in EORTC QLQ-CLL 16 Domain Scores at End of Treatment |
0.1; 0.0; 0.3; 0.1; 0.1; 0.0 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale at End of Treatment |
-4.3; 4.0 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Utility Score Scale at End of Treatment |
0.0; 0.0 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
- Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment
- Measurable nodal disease by computed tomography
- Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
- Eastern Cooperative Oncology Group Performance Status score of 0 or 1
- Hematology and biochemical values within protocol-defined limits
- Agrees to protocol-defined use of effective contraception
- Women of childbearing potential must have negative blood or urine pregnancy test at screening
Exclusion Criteria
- Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy)
- Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
- The presence of deletion of the short arm of chromosome 17
- Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
- Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
- Received a hematopoietic stem cell transplant
- Known central nervous system leukemia/lymphoma or Richter's transformation
- Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- Chronic use of corticosteroids
- History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
- History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
- Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C
- Any uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
- A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
Data sourced from ClinicalTrials.gov (NCT01611090) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.