Ignite Creation Date:
2024-05-05 @ 6:36 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00511121
Status:
TERMINATED
Last Update Posted:
2007-08-03
First Post:
2007-08-02
Brief Title:
Study of the Combination of a Tyrosine Kinase Inhibitor STI571 and a Pegylated Human Recombinant Interferon alfa2b PEGINTRON
Sponsor:
University of Bologna
Organization:
University of Bologna
Study Overview
Official Title:
An Exploratory Phase II Study of the Combination of a Tyrosine Kinase Inhibitor STI571 and a Pegylated Human Recombinant Interferon alfa2b PEGINTRON in the Treatment of Chronic Myeloid Leukemia in Chronic Phase
Status:
TERMINATED
Status Verified Date:
2007-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase II multicenter open-label study designed to investigate the feasibility tolerance compliance and safety of a combination of the tyrosine kinase inhibitor STI 571 GLIVEC Novartis Pharma with a pegylated -Interferon 2b PEG INTRON The rationale for testing this combination is that 1 aIFN is curently the first line agent for the treatment of CML 2 the pegylated formulation of aIFN is more convenient and is better tolerated than the conventional formulation 3 STI571 is currently the most promising investigational agent for the treatment of CML because it is targeted to the molecular bases of the disease is effective also in the advanced phases of the disease and is effective also in the cases who are resistant to aIFN 4 the mechanisms of action of the two agents are different Therefore the combination of STI571 and PEGINTRON is likely to provide the best treatment of CML and to be tested very soon in randomized phase III studies of efficacy So far STI571 and PEGINTRON have been investigated separately The present study is an exploratory study that has been planned with the aim of evaluating the adverse events and the safety of the combination so as to identify a safe and tolerable regime that can be tested prospectively for efficacy in a subsequent randomized phase III study Based on available knowledge and data STI571 is more specific and can be more effective than PEGINTRON Therefore in this exploratory study STI571 is given a priority over PEGINTRON as to dose and dose adaptation Sixty subjects with chronic phase CML previously untreated with any one of study drugs will be enrolled over a 3 months period and will be treated and studied for 12 months The patients can be pretreated with hydroxyurea whenever required hence are treated with STI 571 at a fixed dose 400mg and with PEG-Intron at doses ranging from 50 to 150 g weekly the first cohort of 20 patients at 50 gw the second cohort of 20 patients at 100 gw and the third cohort of 20 patients at 150 gw The response hematologic cytogenetic and molecular to the combination treatment will be evaluated every 3 months and the pharmacokinetics of study drugs will be studied in a sample of study patients The duration of the study is 12 months for a total trial time of 15 months
Detailed Description:
STI 571 and IFN are the two single most effective agents for the treatment of CML Their mechanisms of actions are different Their toxicity is also different but both spare normal hemopoietic stem cells STI 571 is well tolerated while conventional IFN is poorly tolerated especially in the elderly PEG IFNs are going to substitute for conventional IFNs because of a better pharmacokinetic and toxicity profile and because require less injections once a week vs once a dayResistance to IFN 6-13 and to STI571 29-34 occurs in vitro and in vivo where it increases with time for IFN and is also expected to increase with time for STI571 STI571 and IFN have different mechanisms of action and it has been shown in vitro that the combination of STI571 with alfaIFN is more toxic than either agent alone against Ph positive cells 35-37 Therefore a combination of STI 571 with a PEG IFN is worth testing A phase II dose-finding exploratory study is required to investigate feasibility toxicity safety and tolerability of the combination In CML PEG INTRON studies are more advanced than PEGASIS studies These considerations provide the rationale for this phase II study of STI 571 and PEG INTRON in CML
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None