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

Condition(s) targeted: Chronic Myeloid Leukaemia

Intervention: Glivec (Drug); Interferon (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: PETHEMA Foundation

Official(s) and/or principal investigator(s):
Cervantes Francisco, Dr, Study Chair, Affiliation: Hospital Clínic Barcelona

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

Official title: Randomised Multicentre Phase IV Study to Compare Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec® in Combination With Interferon Alpha at Low Doses in the Treatment of Newly-Diagnosed Chronic-Phase Chronic Myeloid Leukaemia

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome:

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 outcome:

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)

Survival (analysed according to intention to treat)

Haematological and non haematological tolerance and safety

Detailed description: Open, prospective, multicentre, phase IV, comparative and randomised study

Minimum age: 18 Years. Maximum age: 72 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. 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).

2. Age between 18 and 72 years (both included).

3. Performance status < 2 on the ECOG scale (see Annex 3).

4. Secure written or oral informed consent in the presence of a witness and consent for biological samples (annexes 5 and 6).

Exclusion Criteria:

1. Criteria of acceleration or blastic crisis (see Annex 7).

2. 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.

3. Administration of other treatments before inclusion in the protocol (a maximum of 3 months of monotherapy with hydroxyurea is permitted).

4. Altered hepatic or renal function (SGOT, SGPT, total bilirubin and creatinine > 1. 5 times the upper limit of normality).

5. 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).

6. Positive serology for HIV.

7. Record of cancer in the last 5 years (barring basal cell skin carcinoma and cervical carcinoma in situ).

8. Pregnancy or breastfeeding

Hospital general de Jerez de la Frontera, Jerez de la Frontera, Spain

Hospital San Pedro de Alcántara, Cáceres, Spain

Hospital comarcal de Valdeorras, O'Barco de Valdeorras, Spain

Hospital Ntra. Sra. Sonsoles, Avila, Spain

Hospital Clínic, Barcelona, Spain

Hospital Sant pau, Barcelona, Spain

Institut Català d'oncología, Barcelona, Spain

Hospital Universitario "Germans Trias i Pujol", Barcelona, Spain

Hospital vall d'Hebrón, Barcelona, Spain

Hospital del Mar, Barcelona, Spain

Complejo Hospitalario Reina Sofía, Córdoba, Spain

Hospital Ruiz de Alda, Granada, Spain

Hospital Juan Ramón Jiménez, Huelva, Spain

Hospital Médico Quirúrgico Ciudad de Jaén, Jaen, Spain

Hospital Juan Canalejo, La Coruña, Spain

Hospital Arnau de Vilanova, Lleida, Spain

Hospital Clínico San Carlos de Madrid, Madrid, Spain

Hospital Ramón y Cajal, Madrid, Spain

Clínica La Concepción, Madrid, Spain

Hospital Doce de Octubre, Madrid, Spain

Clínica Puerta de Hierro, Madrid, Spain

Hospital Universitario Princcipe de Asturias, Madrid, Spain

Hospital Gregorio Marañón, Madrid, Spain

Hospital de Fuenlabrada, Madrid, Spain

Hospital Universitario Morales Meseguer, Murcia, Murcia, Spain

. Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain

Hospital Carlos Haya, Málaga, Spain

Hospital del Río Carrión, Palencia, Spain

Hospital Clínico Universitario de Salamanca, Salamanca, Spain

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Hospital General, Segovia, Spain

Hospital Universitario Virgen del Rocío, Sevilla, Spain

Hospital Joan XXIII, tarragona, Spain

Hospital Universitario la Fe, Valencia, Spain

Hospital Clínico Universitario, Valencia, Spain

Hospital General Universitario, Valencia, Spain

Hospital dr. Peset, Valencia, Spain

Hospital Xeral, Vigo, Spain

Hospital Meixoeiro, Vigo, Spain

Hospital Virgen de la Concha, Zamora, Spain

Hospital Central de Asturias, Oviedo, Asturias, Spain

Hospital Mútua de Terrassa, Terrassa, Barcelona, Spain

Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

Hospital de Mataró, Mataró, Barcelona, Spain

Hospital Universitario de Canarias, Tenerife, Canarias, Spain

Hospital Son Dureta, Palma de Mallorca, Illes balears, Spain

Hospital de Alcorcón, Alcorcón, Madrid, Spain

Hospital Son Llatzer, Palma de Mallorca, Mallorca, Spain

Clínica Universitaria de Navarra, Pamplona, Navarra, Spain

Hospital de Navarra, Pamplona, Navarra, Spain

Hospital Verge de la Cinta, Tortosa, Tarragona, Spain

Pethema Foundation web

Spanish association of Haematology

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Starting date: July 2003
Ending date: December 2007
Last updated: April 15, 2008