OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy)
OPTIM-DASA
A PROSPECTIVE RANDOMIZED PHASE II STUDY EVALUATING THE OPTIMIZATION OF THE RESIDUAL PLASMATIC LEVEL OF DASATINIB (SPRYCEL®) IN PATIENTS NEWLY DIAGNOSED WITH CHRONIC PHASE CHRONIC MYELOGENOUS LEUKAEMIA (CP-CML).
1 other identifier
interventional
289
2 countries
34
Brief Summary
This protocol is a multicentric interventional phase II study from the French CML Intergroup (FILMC). The core of the protocol is to explore the efficacy and safety of an optimization strategy consisting in the modulation of the dasatinib daily dose according to the results of repeated plasmatic levels of dasatinib. The objective of this strategy is to improve the overall results of the treatment of early CP-CML in order to avoid the development of resistance and BCR-ABL tyrosine kinase mutations. The study will be conducted in selected FILMC and Canadian centers. The study is sponsored by the Hôpitaux de Versailles and supported by Bristol-Myers Squibb. The dasatinib treatment will be provided by Bristol-Myers Squibb until marketing authorization is granted in that indication.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2009
Typical duration for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2009
CompletedFirst Submitted
Initial submission to the registry
December 18, 2012
CompletedFirst Posted
Study publicly available on registry
August 6, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2013
CompletedAugust 22, 2016
August 1, 2016
4.6 years
December 18, 2012
August 19, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Cumulative rate of significant AE
The cumulative rate of serious AEs defined by grade 3-4 fluid retention, all grade pleural effusion, haematological grade 3-4 AEs related to dasatinib and/or all AE leading to dasatinib discontinuation within the first year of therapy
12 months therapy
Secondary Outcomes (14)
Rate of treatment interruptions
12 months therapy
Cumulative duration of dasatinib interruption
12 months therapy
Mean dose of dasatinib
12 months therapy
Cumulative rate of complete cytogenetic response
12 months therapy
Cumulative rate of major molecular response
12 months therapy
- +9 more secondary outcomes
Study Arms (3)
A1
EXPERIMENTALArm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake
A2
ACTIVE COMPARATORArm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake
B
ACTIVE COMPARATORArm B : Dasatinib standard dose with Cmin \< 3nM analysed on blood after 7-10 days dasatinib 100mg intake
Interventions
Dasatinib is a multitargeted tyrosine kinase inhibitor with a 300-fold more potent activity on the BCR-ABL tyrosine kinase in vitro compared to imatinib mesylate
Eligibility Criteria
You may qualify if:
- Male or female patient ≥ 18 years
- ECOG Performance Status score 0-2
- Philadelphia chromosome positive newly diagnosed (≤ 3 months) CP-CML
- patients not previously treated except with hydroxyurea or imatinib (less than 4 weeks for imatinib)
- Signed written inform consent
- Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; ALT and AST ≤ 2.5 times the institutional upper limit of normal (ULN).
- Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception.
You may not qualify if:
- Patients with BCR-ABL positive, Philadelphia negative CML
- Patient previously treated with a tyrosine kinase inhibitor (TKI) except with imatinib during less than 4 weeks.
- Pregnancy
- Active malignancy
- Uncontrolled or significant cardiovascular disease
- Patients with QTc \> 450 ms
- Significant bleeding disorder unrelated to CML
- Concurrent severe diseases which exclude the administration of therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Versailles Hospitallead
- Maisonneuve-Rosemont Hospitalcollaborator
- University Hospital, Bordeauxcollaborator
Study Sites (34)
Southern Alberta Cancer Research Institute
Calgary, Canada
Hôpital Charles LeMoyne
Greenfield Park, Canada
Queen elisabeth II Health Sciences Center
Halifax, Canada
CH Pierre LeGardeur
Lachenaie, Canada
Moncton City Hospital
Moncton, Canada
Hôpital Général Juif - Sir. Mortimer B. Davis
Montreal, Canada
Hôpital Maisonneuve-Rosemont
Montreal, Canada
Hôpital Royal Victoria
Montreal, Canada
Hôpital de l'Enfant Jésus - Centre hospitalier affilié universitaire de Québec
Québec, Canada
Pavillon Hôtel-Dieu de Québec - Centre hospitalier universitaire de Québec
Québec, Canada
CHU Angers
Angers, France
Hôpital Avicenne
Bobigny, France
Institut Bergonie
Bordeaux, France
Hopital MORVAN
Brest, France
CH René Dubos
Cergy-Pontoise, France
Hôpital d'Instruction de Armées Percy
Clamart, France
Hopital Henri MONDOR
Créteil, France
Hôpital Claude Huriez
Lille, France
CH Lyon Sud
Lyon, France
Institut Paoli-Calmettes
Marseille, France
Hôpital d'Annecy
Metz-Tessy, France
C.H.U. Brabois
Nancy, France
CHU Hoptel dieu
Nantes, France
Hôpital l'Archet 1
Nice, France
CHU Caremeau
Nîmes, France
Hopital Saint Louis
Paris, France
Hôpital Necker-Enfants Malades
Paris, France
Hôpital St Antoine
Paris, France
CHU Poitiers
Poitiers, France
CHU Rennes - Pontchaillou
Rennes, France
Centre René Huguenin
Saint-Cloud, France
Hôpital Purpan
Toulouse, France
CHRU Bretonneau
Tours, France
Central Hospital
Versailles, France
Related Publications (1)
Rousselot P, Mollica L, Guilhot J, Guerci A, Nicolini FE, Etienne G, Legros L, Charbonnier A, Coiteux V, Dartigeas C, Escoffre-Barbe M, Roy L, Cony-Makhoul P, Dubruille V, Gardembas M, Huguet F, Rea D, Cayssials E, Guilhot F, Bergeron A, Molimard M, Mahon FX, Cayuela JM, Busque L, Bouchet S. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol. 2021 Jul;194(2):393-402. doi: 10.1111/bjh.17654. Epub 2021 Jun 30.
PMID: 34195988DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Philippe ROUSSELOT, Professeur hémato-oncologie
Versailles Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Clinical Coordinator
Study Record Dates
First Submitted
December 18, 2012
First Posted
August 6, 2013
Study Start
May 1, 2009
Primary Completion
December 1, 2013
Study Completion
December 1, 2013
Last Updated
August 22, 2016
Record last verified: 2016-08