Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia

NCT00390897 | Completed Phase 4

• 2 other identifiers: LMC/PETHEMA03-0289
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 51

Brief Summary

To compare the complete cytogenetic response rate in patients with newly-diagnosed chronic-phase chronic myeloid leukaemia treated with Glivec® alone or in combination with interferon at low doses

Conditions

Chronic Myeloid Leukaemia

Keywords

chronic myeloid leukaemia; Glivec; Interferon

Outcome Measures

Primary Outcomes (5)

• The fundamental objective of this study is to compare the therapeutic efficacy of Glivec® given in monotherapy (providing for dose scaling according to the response obtained at different periods of time from the beginning) in combination with standard in

• The median survival of patients with CML is close to 7 years.

• One year and a half after diagnosis, the rate of progression to the acceleration phase and blastic crisis is very low (3.3%) in patients treated with Glivec® as first line.

• With the treatments available hitherto, the achievement of a major cytogenetic response and above all cytogenetic response translates into a prolongation of survival.

• Therefore, taking into account that the rate of complete cytogenetic responses to Glivec® in newly-diagnosed CML is 76% after 18 months of treatment (see table I), the fundamental objective of the study will be to compare the rate of complete cytogenetic

Secondary Outcomes (7)

• The time until complete cytogenetic responses are obtained

• Rate of major cytogenetic responses

• Rate of molecular responses

• Time to the loss of cytogenetic, haematological or molecular response

• Time to the progression of the disease to the phases of acceleration and blastic crisis (analysed according to intention to treat)

Interventions

Glivec DRUG

Interferon DRUG

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly-diagnosed chronic-phase Ph-positive chronic myeloid leukaemia (maximum 3 months as of the diagnosis of the disease, with the date of the cytogenetic study regarded as such).
• Age between 18 and 72 years (both included).
• Performance status \< 2 on the ECOG scale (see Annex 3).
• Secure written or oral informed consent in the presence of a witness and consent for biological samples (annexes 5 and 6).

You may not qualify if:

• Criteria of acceleration or blastic crisis (see Annex 7).
• When there is a compatible family donor in patients aged under 40 years or a non-relative donor in patients aged under 30 years (in whom allogenic transplant is still regarded as first-line treatment), the possibility of performing an allogenic transplant as first therapeutic option should be considered. In any case, as this aspect is still a matter of debate, it is left up to each group to take the relevant decision depending on the institution's policy.
• Altered hepatic or renal function (SGOT, SGPT, total bilirubin and creatinine \> 1.5 times the upper limit of normality).
• Uncontrolled diseases, such as thyroidal dysfunction, diabetes mellitus, angina pectoralis, serious heart failure (functional class III/IV of the New York Heart Association classification), neuropsychiatric infection or disease (see annex 15).
• Positive serology for HIV.
• Record of cancer in the last 5 years (barring basal cell skin carcinoma and cervical carcinoma in situ).
• Pregnancy or breastfeeding

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (51)

Hospital Ntra. Sra. Sonsoles

Ávila, Avila, Spain

Location

Hospital Son Dureta

Palma de Mallorca, Balearic Islands, Spain

Location

Hospital Clínic

Barcelona, Barcelona, Spain

Location

Hospital del Mar

Barcelona, Barcelona, Spain

Location

Hospital Sant pau

Barcelona, Barcelona, Spain

Location

Hospital Universitario "Germans Trias i Pujol"

Barcelona, Barcelona, Spain

Location

Hospital vall d'Hebrón

Barcelona, Barcelona, Spain

Location

Institut Català d'oncología

Barcelona, Barcelona, Spain

Location

Hospital de Mataró

Mataró, Barcelona, Spain

Location

Corporació Sanitària Parc Taulí

Sabadell, Barcelona, Spain

Location

Hospital Mútua de Terrassa

Terrassa, Barcelona, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Location

Complejo Hospitalario Reina Sofía

Córdoba, Córdoba, Spain

Location

Hospital Ruiz de Alda

Granada, Granada, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, Huelva, Spain

Location

Hospital Médico Quirúrgico Ciudad de Jaén

Jaén, Jaen, Spain

Location

Hospital Juan Canalejo

A Coruña, La Coruña, Spain

Location

Hospital Arnau de Vilanova

Lleida, Lleida, Spain

Location

Hospital de Alcorcón

Alcorcón, Madrid, Spain

Location

Clínica La Concepción

Madrid, Madrid, Spain

Location

Clínica Puerta de Hierro

Madrid, Madrid, Spain

Location

Hospital Clínico San Carlos de Madrid

Madrid, Madrid, Spain

Location

Hospital de Fuenlabrada

Madrid, Madrid, Spain

Location

Hospital Doce de Octubre

Madrid, Madrid, Spain

Location

Hospital Gregorio Marañón

Madrid, Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Universitario Princcipe de Asturias

Madrid, Madrid, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Mallorca, Spain

Location

Hospital Universitario Morales Meseguer, Murcia

Murcia, Murcia, Spain

Location

. Hospital Clínico Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Location

Hospital Carlos Haya

Málaga, Málaga, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Location

Hospital de Navarra

Pamplona, Navarre, Spain

Location

Hospital del Río Carrión

Palencia, Palencia, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, Salamanca, Spain

Location

Hospital General

Segovia, Segovia, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Sevilla, Spain

Location

Hospital Joan XXIII

Tarragona, Tarragona, Spain

Location

Hospital Verge de la Cinta

Tortosa, Tarragona, Spain

Location

Hospital Clínico Universitario

Valencia, Valencia, Spain

Location

Hospital dr. Peset

Valencia, Valencia, Spain

Location

Hospital General Universitario

Valencia, Valencia, Spain

Location

Hospital Universitario la Fe

Valencia, Valencia, Spain

Location

Hospital Meixoeiro

Vigo, Vigo, Spain

Location

Hospital Xeral

Vigo, Vigo, Spain

Location

Hospital Virgen de la Concha

Zamora, Zamora, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

Hospital general de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Hospital comarcal de Valdeorras

O'Barco de Valdeorras, Spain

Location

Related Publications (21)

• RUDKIN CT, HUNGERFORD DA, NOWELL PC. DNA CONTENTS OF CHROMOSOME PH1 AND CHROMOSOME 21 IN HUMAN CHRONIC GRANULOCYTIC LEUKEMIA. Science. 1964 Jun 5;144(3623):1229-31. doi: 10.1126/science.144.3623.1229.

  PMID: 14150328 BACKGROUND

• Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973 Jun 1;243(5405):290-3. doi: 10.1038/243290a0. No abstract available.

  PMID: 4126434 BACKGROUND

• Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990 Mar 15;344(6263):251-3. doi: 10.1038/344251a0.

  PMID: 2179728 BACKGROUND

• Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990 Feb 16;247(4944):824-30. doi: 10.1126/science.2406902.

  PMID: 2406902 BACKGROUND

• Goldman JM, Szydlo R, Horowitz MM, Gale RP, Ash RC, Atkinson K, Dicke KA, Gluckman E, Herzig RH, Marmont A, et al. Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase. Blood. 1993 Oct 1;82(7):2235-8.

  PMID: 8400272 BACKGROUND

• Italian Cooperative Study Group on Chronic Myeloid Leukemia; Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, Zaccaria A, Fiacchini M. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5. doi: 10.1056/NEJM199403243301204.

  PMID: 8114834 BACKGROUND

• Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5;344(14):1031-7. doi: 10.1056/NEJM200104053441401.

  PMID: 11287972 BACKGROUND

• Savage DG, Antman KH. Imatinib mesylate--a new oral targeted therapy. N Engl J Med. 2002 Feb 28;346(9):683-93. doi: 10.1056/NEJMra013339. No abstract available.

  PMID: 11870247 BACKGROUND

• Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O'Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E; International STI571 CML Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002 Feb 28;346(9):645-52. doi: 10.1056/NEJMoa011573.

  PMID: 11870241 BACKGROUND

• O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003 Mar 13;348(11):994-1004. doi: 10.1056/NEJMoa022457.

  PMID: 12637609 BACKGROUND

• Kantarjian HM, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Shan J, Rios MB, Cortes J. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003 Jan 15;101(2):473-5. doi: 10.1182/blood-2002-05-1451. Epub 2002 Sep 12.

  PMID: 12393385 BACKGROUND

• Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, Dupriez B, Pigneux A, Choufi B, Reman O, Stephane D, Royer B, Vigier M, Ojeda-Uribe M, Recher C, Dombret H, Huguet F, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chronique; Group for Research in Adult Acute Lymphoblastic Leukemia. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006 Mar;20(3):400-3. doi: 10.1038/sj.leu.2404115.

  PMID: 16437142 BACKGROUND

• Deng M, Daley GQ. Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia. Blood. 2001 Jun 1;97(11):3491-7. doi: 10.1182/blood.v97.11.3491.

  PMID: 11369642 BACKGROUND

• Bhatia R, Wayner EA, McGlave PB, Verfaillie CM. Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J Clin Invest. 1994 Jul;94(1):384-91. doi: 10.1172/JCI117333.

  PMID: 7518835 BACKGROUND

• Thiesing JT, Ohno-Jones S, Kolibaba KS, Druker BJ. Efficacy of STI571, an abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against bcr-abl-positive cells. Blood. 2000 Nov 1;96(9):3195-9.

  PMID: 11050003 BACKGROUND

• Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, Furukawa Y. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood. 2001 Apr 1;97(7):1999-2007. doi: 10.1182/blood.v97.7.1999.

  PMID: 11264164 BACKGROUND

• Kontsioti F, Pappa V, Papasteriadis C, Economopulos T, Dervenoulas J, Papageorgiou E, Kalantzis D, Valsami S, Pappa M, Raptis S. In vitro effect of STI-571 in combination with A-interferon of the proliferation, differentiation and apoptosis of K562 cells. Hematol J 2002; suppl 1:980.

  BACKGROUND

• O´Brien SG, Vallance SE, Craddock C, Holyoake TL, Goldman JM. PEGIntron and STI571 combination evaluation study (PISCES) in chronic phase chronic myeloid leukaemia. Blood 2001; suppl.:3512.

  BACKGROUND

• Trabacchi E, Bassi S, Saglio G, Rege-cambrin G, Bonifazi F, De Vivo A, Testoni N, Martinelli G, Ruggeri D, Amabile M, Giannini B, Alberti D, Fincato GL, Tura S, Rosti G, Baccarani M. Pegylated recombinant interferon alfa 2b (PEGIntron) associated with imatinib mesylate (Glivec) in Ph chronic myeloid leukaemia (CML) in early chronic phase: a phase II study of the ICSG on CML. Hematol J 2002, suppl. :586

  BACKGROUND

• O´Dwyer ME, Mauro MJ, Aust S, Kuyl J, PaquetteR, Sawyers C, Druker BJ. Ongoing evaluation of the combination of imatinib mesylate (Glivectm) with low dose interferon-alpha for the treatment of chronic phase CML. Hematol J 2002; suppl. : 990

  BACKGROUND

• Cervantes F, Lopez-Garrido P, Montero MI, Jonte F, Martinez J, Hernandez-Boluda JC, Calbacho M, Sureda A, Perez-Rus G, Nieto JB, Perez-Lopez C, Roman-Gomez J, Gonzalez M, Pereira A, Colomer D. Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group. Haematologica. 2010 Aug;95(8):1317-24. doi: 10.3324/haematol.2009.021154. Epub 2010 Mar 10.

  PMID: 20220063 DERIVED

Related Links

• Spanish association of Haematology

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; Interferons

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; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Cervantes Francisco, Dr

  Hospital Clinic of Barcelona

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 20, 2006
• First Posted: October 23, 2006
• Study Start: July 1, 2003
• Primary Completion: October 1, 2006
• Study Completion: December 1, 2007
• Last Updated: November 27, 2008

Record last verified: 2008-11

Locations

ES (51)