Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
Recruitment status was Recruiting
This study will investigate the efficacy and tolerability of a short (6 months) high dose therapy followed by a standard dose compared to a continuous treatment with a standard dose of imatinib (Glivec®) in pretreated Philadelphia chromosome- positive (Ph+)/BCR-ABL+ CML patients in chronic phase.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter, Phase III Study Comparing Imatinib (STI571, Glivec®) Standard Dose (400 Mg/Day) With Imatinib High Dose Induction (800 Mg/Day) Followed by Standard Dose Maintenance (400 Mg/Day) in Pretreated CML Patients in Chronic Phase|
- To determine the efficacy regarding major cytogenetic response within 12 months after randomization
- To determine the major cytogenetic response after 3 months versus 6-12 months after randomization
- To determine the efficacy of the molecular response within 12 and 24 months after randomization
- To determine the time to molecular progression within 24 months
- To determine the dynamics of the molecular response within 3 and 6 months after randomization expressed as the slope decreases in BCR-ABL-transcripts
- To determine tolerability
|Study Start Date:||January 2004|
|Estimated Study Completion Date:||December 2008|
Patients with CML not achieving or losing a major cytogenetic response on whatever palliative treatment for CML, are at high risk to progress to accelerated phase and blast crisis. A new promising treatment with Imatinib (Glivec®), a tyrosine-kinase inhibitor, has been introduced recently. High rates of hematologic and cytogenetic responses can be achieved with Imatinib (Glivec®) at > = 300 mg/day in chronic phase CML patients that are refractory, resistant or intolerant to interferon-alpha. However, about 10 – 20% of these high risk patients will lose their response to Imatinib (Glivec®) within 1-2 years. Therefore, improvement of the treatment is warranted.
Since cytogenetic response rate is correlated to survival and the resistance to Imatinib (Glivec®) might be caused by mutations in the receptor, a more rapid decrease could lead to longer survival and/or less resistance development. In the initial 6 months of treatment, monotherapy with Imatinib (Glivec®) with a dose of 800 mg/day (high dose) should be more effective in the reduction of a high leukemic tumor burden, thereby allowing the residual normal progenitor and stem cells to expand. In addition, high dose Imatinib (Glivec®) should further improve the induction of a molecular response, as determined by quantitative reverse transcription polymerase chain reaction (RT-PCR), reducing the risk of relapse from residual malignant BCR-ABL positive cells.
This study will investigate the efficacy and tolerability of a short (6 months) high dose therapy followed by a standard dose compared to a continuous treatment with a standard dose of Imatinib (Glivec®).
In addition, the dynamics of the molecular and cytogenetic response will be investigated. Finally, the study will investigate the effect of this induction-maintenance concept on time-to-progression (TTP).
|Contact: Guenther Gastl, MD||++43 512 504 firstname.lastname@example.org|
|Medical University Innsbruck||Recruiting|
|Innsbruck, Tyrol, Austria, 6020|
|Contact: Guenther Gastl, MD|
|Contact: Dominic Fong, MD|
|Principal Investigator: Guenther Gastl, MD|
|Study Chair:||Guenther Gastl, MD||Medical University Innsbruck|