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

The Lancet Oncology

Volumn 17, Issue 2, 2016, Pages 200-211

  Chanan Khan, Asher ^a   Cramer, Paula ^b   Demirkan, Fatih ^c   Fraser, Graeme ^d   Silva, Rodrigo Santucci ^e   Grosicki, Sebastian ^f   Pristupa, Aleksander ^g   Janssens, Ann ^h   Mayer, Jiri ⁱ   Bartlett, Nancy L ^j   Dilhuydy, Marie Sarah ^k   Pylypenko, Halyna ^l   Loscertales, Javier ^m   Avigdor, Abraham ⁿ   Rule, Simon ^o   Villa, Diego ^p   Samoilova, Olga ^q   Panagiotidis, Panagiots ^r   Goy, Andre ^s   Mato, Anthony ^s,t   Pavlovsky, Miguel A ^u   Karlsson, Claes ^v   Mahler, Michelle ^w   Salman, Mariya ^w   Sun, Steven ^w   Phelps, Charles ^w   Balasubramanian, Sriram ^x   Howes, Angela ^x   Hallek, Michael ^b   more..

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF COLOGNE   (Germany)

^c DOKUZ EYLUL UNIVERSITY   (Turkey)

^d MCMASTER UNIVERSITY   (Canada)

^e Hemomed Instituto de Oncologia e Hematologia   (Brazil)

^f MEDICAL UNIVERSITY OF SILESIA   (Poland)

^g Ryazan Regional Clinical Hospital   (Russian Federation)

^h UNIVERSITY HOSPITALS LEUVEN   (Belgium)

ⁱ UNIVERSITY HOSPITAL BRNO   (Czech Republic)

^j USA   (United States)

^k HAUT LÉVÊQUE HOSPITAL   (France)

^l Regional Oncological Center   (Ukraine)

^m HOSPITAL UNIVERSITARIO DE LA PRINCESA   (Spain)

ⁿ TEL AVIV UNIVERSITY   (Israel)

^o DERRIFORD HOSPITAL   (United Kingdom)

^p BRITISH COLUMBIA CANCER AGENCY   (Canada)

^q Nizhny Novogorod Regional Clinical Hospital   (Russian Federation)

^r UNIVERSITY OF ATHENS   (Greece)

^s HACKENSACK UNIVERSITY MEDICAL CENTER   (United States)

^t UNIVERSITY OF PENNSYLVANIA   (United States)

^u Department of Hematology ^*  (Argentina)

^v KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^w JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^x JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BENDAMUSTINE; IBRUTINIB; PLACEBO; RITUXIMAB; ANTINEOPLASTIC AGENT; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ABDOMINAL PAIN; ADULT; ANEMIA; ARTHRALGIA; ARTICLE; ATRIAL FIBRILLATION; BACKACHE; BLEEDING; BLURRED VISION; BONE MARROW; BRONCHITIS; CANCER SIZE; CATARACT; CHILL; CHRONIC LYMPHATIC LEUKEMIA; COMPUTER ASSISTED TOMOGRAPHY; CONSTIPATION; CONTROLLED STUDY; CONTUSION; COUGHING; CROSSOVER PROCEDURE; DECREASED APPETITE; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS; ECCHYMOSIS; EPISTAXIS; EYE DISEASE; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; FOLLOW UP; FUNCTIONAL STATUS ASSESSMENT; HEADACHE; HEART ATRIUM FLUTTER; HEMATOMA; HUMAN; HYPERURICEMIA; INFUSION RELATED REACTION; INTENTION TO TREAT ANALYSIS; INTERNATIONAL COOPERATION; KIDNEY FUNCTION; LEUKEMIA RELAPSE; LIVER FUNCTION; LYMPH NODE METASTASIS; LYMPHOCYTOMA; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MUSCLE SPASM; NAUSEA; NEUTROPENIA; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PERIPHERAL EDEMA; PETECHIA; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; RISK BENEFIT ANALYSIS; SURVIVAL TIME; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; VOMITING; AGED; CHEMICALLY INDUCED; CLINICAL TRIAL; COMPARATIVE STUDY; DISEASE COURSE; DISEASE FREE SURVIVAL; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; RETREATMENT; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANEMIA; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ATRIAL FIBRILLATION; BENDAMUSTINE HYDROCHLORIDE; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; FEMALE; HEMORRHAGE; HUMANS; INTENTION TO TREAT ANALYSIS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; NAUSEA; NEUTROPENIA; PYRAZOLES; PYRIMIDINES; RETREATMENT; RITUXIMAB; THROMBOCYTOPENIA;

EID: 84959366494     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(15)00465-9     Document Type: Article

References (22)

1. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014, 370:1101-1110.
2. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010, 376:1164-1174.
3. Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 2008, 112:975-980.
4. Eichhorst B, Dreyling M, Robak T, et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011, 22:vi50-vi54.
5. NCCN non-Hodgkin lymphoma guidelines National Comprehensive Cancer Network, (accessed Feb 3, 2015). http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf.
6. Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2011, 29:3559-3566.
7. Buggy JJ, Elias L Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol 2012, 31:119-132.
8. Chang BY, Francesco M, De Rooij MF, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood 2013, 122:2412-2424.
9. Cinar M, Hamedani F, Mo Z, et al. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Leuk Res 2013, 37:1271-1277.
10. de Rooij MFM, Kuil A, Geest C, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor-and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 2012, 119:2590-2594.
11. Herman SE, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 2011, 117:6287-6296.
12. Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in modes of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA 2010, 107:13075-13080.
13. Ponader S, Chen SS, Buggy JJ, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 2012, 119:1182-1189.
14. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013, 369:32-42.
15. Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015, 125:2497-2506.
16. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014, 371:213-223.
17. Brown JR, Barrientos JC, Barr PM, et al. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood 2015, 125:2915-2922.
18. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008, 111:5446-5456.
19. Rawstron AC, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007, 21:956-964.
20. Ishak KJ, Proskorovsky I, Korytowsky B, et al. Methods for adjusting for bias due to crossover in oncology trials. Pharmacoeconomics 2014, 32:533-546.
21. Rosenwald A, Alizadeh AA, Widhopf G, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001, 194:1639-1647.
22. Fisher RI Advanced insights into the biology of malignant lymphomas. J Clin Oncol 2011, 29:1799-1800.