Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL

Leukemia

Volumn 31, Issue 10, 2017, Pages 2085-2093

  Munir, T ^a   Howard, D R ^b   McParland, L ^b   Pocock, C ^c   Rawstron, A C ^a   Hockaday, A ^b   Varghese, A ^a   Hamblin, M ^d   Bloor, A ^e   Pettitt, A ^f   Fegan, C ^g   Blundell, J ^h   Gribben, J G ⁱ   Phillips, D ^b   Hillmen, P ^b  

^a ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

^b UNIVERSITY OF LEEDS   (United Kingdom)

^c EAST KENT HOSPITALS UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

^d IPSWICH HOSPITAL NHS TRUST   (United Kingdom)

^e CHRISTIE HOSPITAL   (United Kingdom)

^f UNIVERSITY OF LIVERPOOL   (United Kingdom)

^g UNIVERSITY HOSPITAL OF WALES   (United Kingdom)

^h ROYAL CORNWALL HOSPITAL   (United Kingdom)

ⁱ BARTS HEALTH NHS TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPHOSPHAMIDE; FLUDARABINE; GRANULOCYTE COLONY STIMULATING FACTOR; MITOXANTRONE; RITUXIMAB; ANTINEOPLASTIC AGENT; VIDARABINE;

AGED; ARTICLE; BONE MARROW HYPOPLASIA; BONE MARROW SUPPRESSION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; FEMALE; GASTROINTESTINAL DISEASE; HEART DISEASE; HEMATOLOGIC DISEASE; HEPATOBILIARY DISEASE; HUMAN; INFECTION; INFESTATION; LEUKEMIA REMISSION; LYMPHATIC SYSTEM DISEASE; MAJOR CLINICAL STUDY; MALE; MEDIASTINUM DISEASE; MINIMAL RESIDUAL DISEASE; MULTICENTER STUDY; NEUTROPENIA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; THORAX DISEASE; URINARY TRACT DISEASE; ADULT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; COMPARATIVE STUDY; DISEASE FREE SURVIVAL; KAPLAN MEIER METHOD; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; REMISSION; SURVIVAL RATE; TREATMENT OUTCOME;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CYCLOPHOSPHAMIDE; DISEASE-FREE SURVIVAL; FEMALE; GRANULOCYTE COLONY-STIMULATING FACTOR; HUMANS; KAPLAN-MEIER ESTIMATE; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; MITOXANTRONE; NEOPLASM, RESIDUAL; NEUTROPENIA; REMISSION INDUCTION; RITUXIMAB; SURVIVAL RATE; TREATMENT OUTCOME; VIDARABINE;

EID: 85030636943     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2017.65     Document Type: Article

References (22)

1. Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016; 127: 208-215
2. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, 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, Kantarjian H, Wen S, Do KA, 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. Wilder DD, Ogden JL, Jain VK. Efficacy of fludarabine/mitoxantrone/dexamethasone alternating with CHOP in bulky follicular non-Hodgkin's lymphoma. Clin Lymphoma 2002; 2: 229-237
5. Zinzani PL, Magagnoli M, Moretti L, Battista R, Ronconi F, De Renzo A, et al. Fludarabine based chemotherapy in untreated mantle cell lymphomas: an encouraging experience in 29 patients. Haematologica 1999; 84: 1002-1006
6. Bosch F, Ferrer A, Villamor N, Gonzalez M, Briones J, Gonzalez-Barca E, et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: High response rate and disease eradication. Clin Cancer Res 2008; 14: 155-161
7. Bosch F, Abrisqueta P, Villamor N, Terol MJ, Gonzalez-Barca E, Ferra C, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol 2009; 27: 4578-4584
8. Bosch F, Ferrer A, Lopez-Guillermo A, Gine E, Bellosillo B, Villamor N, et al. Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. Br J Haematol 2002; 119: 976-984
9. Hendry L, Bowen A, Matutes E, Swansbury J, Catovsky D. Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma. Leuk Lymphoma 2004; 45: 945-950
10. Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, et al. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol 2011; 152: 570-578
11. Kwok M, Rawstron AC, Varghese A, Hillmen P. Minimal residual disease is a predictor for progression-free and overall survival in chronic lymphocytic leukemia (CLL) that is independent of the type or line of therapy. Blood 2009; 114: 226
12. Rawstron AC, Kennedy B, Evans PAS, Davies FE, Richards SJ, Haynes AP, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98: 29-35
13. Rawstron AC, Villamor N, Ritgen M, Boettcher S, Ghia P, Zehnder JL, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007; 21: 956-964
14. Böttcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol 2012; 30: 980-988
15. Kwok M, Rawstron A, Varghese A, Evans P, O'Connor S, Doughty C, et al. Independent prognostic significance of minimal residual disease status in chronic lymphocytic leukaemia. Lancet 383: S66
16. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, 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
17. Dearden CE, Richards S, Else M, Catovsky D, Hillmen P. A comparison of the efficacy and safety of oral and intravenous fludarabine in chronic lymphocytic leukemia in the LRF CLL4 trial. Cancer 2011; 117: 2452-2460
18. Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events 2006. v3.0. Available from: http://ctep.cancer.gov/protocolDevelopment/electronic-applications/docs/ctcaev3.pdf
19. Royston P, Parmar MKB. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med 2011; 30: 2409-2421
20. Moher D, Schulz KF, Altman DG, Grp C. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001; 357: 1191-1194
21. Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood 2016; 127: 303-309
22. Howard DR, Munir T, McParland L, Rawstron AC, Milligan D, Schuh A, et al. Results of the randomized phase IIB ARCTIC trial of low dose rituximab in previously untreated CLL. Leukaemia 2017; e-pub ahead of print 24 March 2017; doi: 10.1038/leu.2017.96