Imatinib Standard Dose (400 mg/Day) Versus Imatinib High Dose (800 mg/Day)

Conditions

Chronic Myeloid Leukemia

Keywords

chronic myeloid leukemia, STI 571, CML022

Brief summary

This is a phase III multicenter, open-label study designed to investigate the efficacy (hematological response, cytogenetic response and molecular response) and feasibility (tolerance, compliance and safety) of the tyrosine kinase inhibitor imatinib mesylate (formerly STI 571, GLIVEC, Novartis Pharma) at conventional dose (400 mg/daily) if compared with high dose (800 mg/daily) (serial number protocol ICSG/CML/022) in patients with Ph+ chronic myeloid leukemia (CML) in chronic phase (CP) previously untreated, at high Sokal risk.

Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Fabio Stagno, Giorgina Specchia et al. (30 authors)

Blood2018-11-2910 citations

10.1182/blood-2018-99-117409

Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia

Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Francesco Albano, Alessandra Iurlo et al. (28 authors)

Haematologica2017-06-0121 citations

10.3324/haematol.2017.169532

The BCR‐ABL1 transcript type influences response and outcome in<scp>P</scp>hiladelphia chromosome‐positive chronic myeloid leukemia patients treated frontline with imatinib

Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Luciano Levato et al. (31 authors)

American Journal of Hematology2017-05-0391 citations

10.1002/ajh.24774

Long-Term Outcome to First-Line Imatinib according to 2013 European LeukemiaNet Response Criteria: a GIMEMA CML WP Analysis

Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Fabio Stagno, Alessandra Iurlo et al. (30 authors)

Blood2015-12-032 citations

10.1182/blood.v126.23.2792.2792

Differences among young adults, adults and elderly chronic myeloid leukemia patients.

Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G, GIMEMA CML Working Party.

2014-10-3066 citations

10.1093/annonc/mdu490

Frontline Treatment With Imatinib Mesylate in Chronic Myeloid Leukemia Patients in Early Chronic Phase: a Very Long-Term Analysis by the GIMEMA CML Working Party

Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Giorgina Specchia, Tamara Intermesoli et al. (25 authors)

Blood2013-11-152 citations

10.1182/blood.v122.21.258.258

The e13a2 BCR-ABL1 Fusion Transcript Is a Candidate Adverse Prognostic Factor In Chronic Myeloid Leukemia Patients Treated Frontline With Imatinib Mesylate

Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Elisabetta Abruzzese et al. (25 authors)

Blood2013-11-151 citations

10.1182/blood.v122.21.1486.1486

Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party.

Gugliotta G, Castagnetti F, Palandri F, Breccia M, Intermesoli T, Capucci A, Martino B, Pregno P, Rupoli S, Ferrero D, Gherlinzoni F, Montefusco E, Bocchia M, Tiribelli M, Pierri I, Grifoni F, Marzocchi G, Amabile M, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M, Rosti G, Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party.

2011-03-3075 citations

10.1182/blood-2010-12-324228

Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis.

Marzocchi G, Castagnetti F, Luatti S, Baldazzi C, Stacchini M, Gugliotta G, Amabile M, Specchia G, Sessarego M, Giussani U, Valori L, Discepoli G, Montaldi A, Santoro A, Bonaldi L, Giudici G, Cianciulli AM, Giacobbi F, Palandri F, Pane F, Saglio G, Martinelli G, Baccarani M, Rosti G, Testoni N, Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Working Party on Chronic Myeloid Leukemia.

2011-03-2978 citations

10.1182/blood-2011-01-328294

Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP.

Testoni N, Marzocchi G, Luatti S, Amabile M, Baldazzi C, Stacchini M, Nanni M, Rege-Cambrin G, Giugliano E, Giussani U, Abruzzese E, Kerim S, Grimoldi MG, Gozzetti A, Crescenzi B, Carcassi C, Bernasconi P, Cuneo A, Albano F, Fugazza G, Zaccaria A, Martinelli G, Pane F, Rosti G, Baccarani M.

2009-10-0151 citations

10.1182/blood-2009-07-229864

Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study.

Baccarani M, Rosti G, Castagnetti F, Haznedaroglu I, Porkka K, Abruzzese E, Alimena G, Ehrencrona H, Hjorth-Hansen H, Kairisto V, Levato L, Martinelli G, Nagler A, Lanng Nielsen J, Ozbek U, Palandri F, Palmieri F, Pane F, Rege-Cambrin G, Russo D, Specchia G, Testoni N, Weiss-Bjerrum O, Saglio G, Simonsson B.

2009-03-04136 citations

10.1182/blood-2008-12-191254

Interventions

DRUGSTI571 (400 mg/day; or 800 mg/day)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Age \>/=18 years 2. First chronic phase, less than 6 months of duration 3. High Sokal's risk 4. Ph positive 5. No previous treatment or hydroxiurea only. 6. Performance status (ECOG/WHO) \< 2 7. Written informed consent

Exclusion criteria

1. Age \<18 2. Low or intermediate Sokal risk score. 3. More than 6 months from diagnosis. 4. Second chronic, accelerated or blastic phase 5. Scheduled allogeneic stem cell transplantation within 1 year from diagnosis. 6. Performance status (ECOG/WHO) \> 2 7. Inability to provide written informed consent 8. Pregnancy 9. Formal refusal of any recommendation of a safe contraception 10. Alcohol or drug addiction 11. Altered hepatic or renal function as defined by AST/ALT or bilirubine \> 3 times upper normal limits (UNL) and by creatinine \> 20mg/L 12. Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioural problems.

Design outcomes

Primary

Measure	Time frame
To determine the rate of complete cytogenetic response at 12 months in adult patients with previously untreated high Sokal risk CML treated with imatinib at 2 different dose levels of 400 and 800 mg/daily.	—

Secondary

Measure	Time frame
The rate of major cytogenetic response,the kinetic and duration of cytogenetic response, the time to accelerated and blast crisis and overall survival,safety and tolerability of the treatment.	—

Countries

Italy

Outcome results

None listed