Clinical trial NCT01916785: OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myelogenous Leukemia, BCR/ABL Positive
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
Collaborators: name: Maisonneuve-Rosemont Hospital
name: University Hospital, Bordeaux
First posted: 2013-08-06
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male or female patient ≥ 18 years
2. ECOG Performance Status score 0-2
3. Philadelphia chromosome positive newly diagnosed (≤ 3 months) CP-CML
4. patients not previously treated except with hydroxyurea or imatinib (less than 4 weeks for imatinib)
5. Signed written inform consent
6. 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).
7. Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN.
8. Women of childbearing potential (WOCBP) must be using an adequate method of contraception.

Exclusion Criteria:

1. Patients with BCR-ABL positive, Philadelphia negative CML
2. Patient previously treated with a tyrosine kinase inhibitor (TKI) except with imatinib during less than 4 weeks.
3. Pregnancy
4. Active malignancy
5. Uncontrolled or significant cardiovascular disease
6. Patients with QTc \> 450 ms
7. Significant bleeding disorder unrelated to CML
8. Concurrent severe diseases which exclude the administration of therapy

Primary outcomes:
measure: Cumulative rate of significant AE
timeFrame: 12 months therapy
Secondary outcomes:
measure: Rate of treatment interruptions
timeFrame: 12 months therapy
measure: Cumulative duration of dasatinib interruption
timeFrame: 12 months therapy
measure: Mean dose of dasatinib
timeFrame: 12 months therapy
measure: Cumulative rate of complete cytogenetic response
timeFrame: 12 months therapy
measure: Cumulative rate of major molecular response
timeFrame: 12 months therapy
measure: Median dose of dasatinib administered
timeFrame: 12 months therapy
measure: Cumulative rate of complete molecular response
timeFrame: 12 months therapy
measure: Time to molecular response
timeFrame: 12 months therapy
measure: Relationship between peak plasmatic level and efficacy
timeFrame: 12 months therapy
measure: Relationship between through plasmatic level and efficacy
timeFrame: 12 months therapy
measure: Progression-free survival at 5 years
timeFrame: 12 months therapy
measure: Overall survival at 5 years
timeFrame: 12 months therapy
measure: Lymphocyte populations before and during dasatinib therapy
timeFrame: 12 months therapy
measure: Rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response
timeFrame: 12 months therapy
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Southern Alberta Cancer Research Institute
city: Greenfield Park
country: Canada
facility: Hôpital Charles LeMoyne
city: Halifax
country: Canada
facility: Queen elisabeth II Health Sciences Center
city: Lachenaie
country: Canada
facility: CH Pierre LeGardeur
city: Moncton
country: Canada
facility: Moncton City Hospital
city: Montréal
country: Canada
facility: Hôpital Général Juif - Sir. Mortimer B. Davis
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
city: Montréal
country: Canada
facility: Hôpital Royal Victoria
city: Québec
country: Canada
facility: Hôpital de l'Enfant Jésus - Centre hospitalier affilié universitaire de Québec
city: Québec
country: Canada
facility: Pavillon Hôtel-Dieu de Québec - Centre hospitalier universitaire de Québec
city: Angers
country: France
facility: CHU Angers
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: Hopital MORVAN
city: Cergy Pontoise
country: France
facility: CH René Dubos
city: Clamart
country: France
facility: Hôpital d'Instruction de Armées Percy
city: Creteil
country: France
facility: Hopital Henri MONDOR
city: Lille
country: France
facility: Hôpital Claude Huriez
city: Lyon
country: France
facility: CH Lyon Sud
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Metz Tessy
country: France
facility: Hôpital d'Annecy
city: Nancy
country: France
facility: C.H.U. Brabois
city: Nantes
country: France
facility: CHU Hoptel dieu
city: Nice
country: France
facility: Hôpital l'Archet 1
city: Nimes
country: France
facility: CHU Caremeau
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: Hôpital St Antoine
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes - Pontchaillou
city: Saint Cloud
country: France
facility: Centre René Huguenin
city: Toulouse
country: France
facility: Hôpital Purpan
city: Tours
country: France
facility: CHRU Bretonneau
city: Versailles
country: France
facility: Central Hospital
Study officials:
affiliation: Versailles Hospital
name: Philippe ROUSSELOT, Professeur hémato-oncologie
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.