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

NCT00514488 | Completed Phase 3

• 1 other identifier: ICSG/CML022
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia

Keywords

chronic myeloid leukemia; STI 571; CML022

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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.

Interventions

STI571 (400 mg/day; or 800 mg/day) DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Age \<18
• Low or intermediate Sokal risk score.
• More than 6 months from diagnosis.
• Second chronic, accelerated or blastic phase
• Scheduled allogeneic stem cell transplantation within 1 year from diagnosis.
• Performance status (ECOG/WHO) \> 2
• Inability to provide written informed consent
• Pregnancy
• Formal refusal of any recommendation of a safe contraception
• Alcohol or drug addiction
• Altered hepatic or renal function as defined by AST/ALT or bilirubine \> 3 times upper normal limits (UNL) and by creatinine \> 20mg/L
• 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.

Sponsors & Collaborators

• University of Bologna: lead
• Novartis: collaborator

Study Sites (1)

Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli"

Bologna, Italy

Location

Related Publications (7)

• Gugliotta G, Castagnetti F, Breccia M, Albano F, Iurlo A, Intermesoli T, Abruzzese E, Levato L, D'Adda M, Pregno P, Cavazzini F, Stagno F, Martino B, La Barba G, Sora F, Tiribelli M, Bigazzi C, Binotto G, Bonifacio M, Caracciolo C, Soverini S, Foa R, Cavo M, Martinelli G, Pane F, Saglio G, Baccarani M, Rosti G; Gruppo Italiano Malattie Ematologiche dell'Adulto - Chronic Myeloid Leukemia Working Party. Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia. Haematologica. 2017 Sep;102(9):1530-1536. doi: 10.3324/haematol.2017.169532. Epub 2017 Jun 1.

  PMID: 28572163 DERIVED

• 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. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015 Jan;26(1):185-192. doi: 10.1093/annonc/mdu490. Epub 2014 Oct 30.

  PMID: 25361995 DERIVED

• Luatti S, Castagnetti F, Marzocchi G, Baldazzi C, Gugliotta G, Iacobucci I, Specchia G, Zanatta L, Rege-Cambrin G, Mancini M, Abruzzese E, Zaccaria A, Grimoldi MG, Gozzetti A, Ameli G, Capucci MA, Palka G, Bernasconi P, Palandri F, Pane F, Saglio G, Martinelli G, Rosti G, Baccarani M, Testoni N; Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Working Party on CML. Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis. Blood. 2012 Jul 26;120(4):761-7. doi: 10.1182/blood-2011-10-384651. Epub 2012 Jun 12.

  PMID: 22692507 DERIVED

• 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. Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party. Blood. 2011 May 26;117(21):5591-9. doi: 10.1182/blood-2010-12-324228. Epub 2011 Mar 30.

  PMID: 21450900 DERIVED

• 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. Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis. Blood. 2011 Jun 23;117(25):6793-800. doi: 10.1182/blood-2011-01-328294. Epub 2011 Mar 29.

  PMID: 21447834 DERIVED

• 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. 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. Blood. 2009 Dec 3;114(24):4939-43. doi: 10.1182/blood-2009-07-229864. Epub 2009 Oct 1.

  PMID: 19797518 DERIVED

• 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. 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. Blood. 2009 May 7;113(19):4497-504. doi: 10.1182/blood-2008-12-191254. Epub 2009 Mar 4.

  PMID: 19264678 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Michele Baccarani, MD

  Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 9, 2007
• First Posted: August 10, 2007
• Study Start: June 1, 2004
• Last Updated: August 10, 2007

Record last verified: 2007-07

Locations

IT (1)