Back to resultsOPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy) (OPTIM-DASA)
Primary Purpose
Chronic Myelogenous Leukemia, BCR/ABL Positive
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelogenous Leukemia, BCR/ABL Positive
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Southern Alberta Cancer Research Institute
- Hôpital Charles LeMoyne
- Queen elisabeth II Health Sciences Center
- CH Pierre LeGardeur
- Moncton City Hospital
- Hôpital Général Juif - Sir. Mortimer B. Davis
- Hôpital Maisonneuve-Rosemont
- Hôpital Royal Victoria
- Hôpital de l'Enfant Jésus - Centre hospitalier affilié universitaire de Québec
- Pavillon Hôtel-Dieu de Québec - Centre hospitalier universitaire de Québec
- CHU Angers
- Hôpital Avicenne
- Institut Bergonie
- Hopital MORVAN
- CH René Dubos
- Hôpital d'Instruction de Armées Percy
- Hopital Henri MONDOR
- Hôpital Claude Huriez
- CH Lyon Sud
- Institut Paoli-Calmettes
- Hôpital d'Annecy
- C.H.U. Brabois
- CHU Hoptel dieu
- Hôpital l'Archet 1
- CHU Caremeau
- Hopital Saint Louis
- Hôpital Necker-Enfants Malades
- Hôpital St Antoine
- CHU Poitiers
- CHU Rennes - Pontchaillou
- Centre René Huguenin
- Hôpital Purpan
- CHRU Bretonneau
- Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
A1
A2
B
Arm Description
Arm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake
Arm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake
Arm B : Dasatinib standard dose with Cmin < 3nM analysed on blood after 7-10 days dasatinib 100mg intake
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Rate of treatment interruptions
To compare the rate of treatment interruptions
Cumulative duration of dasatinib interruption
To compare the cumulative duration of dasatinib interruption C. To compare the median dose of dasatinib administered during the first 12 months
Mean dose of dasatinib
To compare the mean dose of dasatinib administered during the first 12 months
Cumulative rate of complete cytogenetic response
To compare the cumulative rate of complete cytogenetic response (CCR) at 6, 12 and 18 months, and every 12 months thereafter
Cumulative rate of major molecular response
To compare the cumulative rate of major molecular response (MMR) at 3, 6, 12, and 18 months, and every 6 months thereafter
Median dose of dasatinib administered
To compare the median dose of dasatinib administered during the first 12 months
Cumulative rate of complete molecular response
To compare the cumulative rate of complete molecular response at 3, 6, 12 and 18 months, and every 6 months thereafter
Time to molecular response
To compare the time to molecular response (major or complete)
Relationship between peak plasmatic level and efficacy
To analyse the relationship between peak plasmatic level (Cmax) and efficacy in the three arms
Relationship between through plasmatic level and efficacy
To analyse the relationship between through plasmatic level (Cmin) and efficacy in the three arms
Progression-free survival at 5 years
To compare the progression-free survival (PFS) at 5 years in the three arms
Overall survival at 5 years
To compare the overall survival at 5 years in the three arms
Lymphocyte populations before and during dasatinib therapy
To analyse lymphocyte populations before and during dasatinib therapy (for French participating centers - see appendix 14).
Rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response
To evaluate the rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response, CMR (undetectable BCR-ABL transcript, BCR-ABL/ABL IS ratio < 1x10-5)
Full Information
NCT ID
NCT01916785
First Posted
December 18, 2012
Last Updated
August 19, 2016
Sponsor
Versailles Hospital
Collaborators
Maisonneuve-Rosemont Hospital, University Hospital, Bordeaux
1. Study Identification
Unique Protocol Identification Number
NCT01916785
Brief Title
OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy)
Acronym
OPTIM-DASA
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
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Versailles Hospital
Collaborators
Maisonneuve-Rosemont Hospital, University Hospital, Bordeaux
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia, BCR/ABL Positive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
289 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A1
Arm Type
Experimental
Arm Description
Arm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake
Arm Title
A2
Arm Type
Active Comparator
Arm Description
Arm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake
Arm Title
B
Arm Type
Active Comparator
Arm Description
Arm B : Dasatinib standard dose with Cmin < 3nM analysed on blood after 7-10 days dasatinib 100mg intake
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
Sprycel®
Intervention Description
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
Primary Outcome Measure Information:
Title
Cumulative rate of significant AE
Description
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
Time Frame
12 months therapy
Secondary Outcome Measure Information:
Title
Rate of treatment interruptions
Description
To compare the rate of treatment interruptions
Time Frame
12 months therapy
Title
Cumulative duration of dasatinib interruption
Description
To compare the cumulative duration of dasatinib interruption C. To compare the median dose of dasatinib administered during the first 12 months
Time Frame
12 months therapy
Title
Mean dose of dasatinib
Description
To compare the mean dose of dasatinib administered during the first 12 months
Time Frame
12 months therapy
Title
Cumulative rate of complete cytogenetic response
Description
To compare the cumulative rate of complete cytogenetic response (CCR) at 6, 12 and 18 months, and every 12 months thereafter
Time Frame
12 months therapy
Title
Cumulative rate of major molecular response
Description
To compare the cumulative rate of major molecular response (MMR) at 3, 6, 12, and 18 months, and every 6 months thereafter
Time Frame
12 months therapy
Title
Median dose of dasatinib administered
Description
To compare the median dose of dasatinib administered during the first 12 months
Time Frame
12 months therapy
Title
Cumulative rate of complete molecular response
Description
To compare the cumulative rate of complete molecular response at 3, 6, 12 and 18 months, and every 6 months thereafter
Time Frame
12 months therapy
Title
Time to molecular response
Description
To compare the time to molecular response (major or complete)
Time Frame
12 months therapy
Title
Relationship between peak plasmatic level and efficacy
Description
To analyse the relationship between peak plasmatic level (Cmax) and efficacy in the three arms
Time Frame
12 months therapy
Title
Relationship between through plasmatic level and efficacy
Description
To analyse the relationship between through plasmatic level (Cmin) and efficacy in the three arms
Time Frame
12 months therapy
Title
Progression-free survival at 5 years
Description
To compare the progression-free survival (PFS) at 5 years in the three arms
Time Frame
12 months therapy
Title
Overall survival at 5 years
Description
To compare the overall survival at 5 years in the three arms
Time Frame
12 months therapy
Title
Lymphocyte populations before and during dasatinib therapy
Description
To analyse lymphocyte populations before and during dasatinib therapy (for French participating centers - see appendix 14).
Time Frame
12 months therapy
Title
Rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response
Description
To evaluate the rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response, CMR (undetectable BCR-ABL transcript, BCR-ABL/ABL IS ratio < 1x10-5)
Time Frame
12 months therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe ROUSSELOT, Professeur hémato-oncologie
Organizational Affiliation
Versailles Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southern Alberta Cancer Research Institute
City
Calgary
Country
Canada
Facility Name
Hôpital Charles LeMoyne
City
Greenfield Park
Country
Canada
Facility Name
Queen elisabeth II Health Sciences Center
City
Halifax
Country
Canada
Facility Name
CH Pierre LeGardeur
City
Lachenaie
Country
Canada
Facility Name
Moncton City Hospital
City
Moncton
Country
Canada
Facility Name
Hôpital Général Juif - Sir. Mortimer B. Davis
City
Montréal
Country
Canada
Facility Name
Hôpital Maisonneuve-Rosemont
City
Montréal
Country
Canada
Facility Name
Hôpital Royal Victoria
City
Montréal
Country
Canada
Facility Name
Hôpital de l'Enfant Jésus - Centre hospitalier affilié universitaire de Québec
City
Québec
Country
Canada
Facility Name
Pavillon Hôtel-Dieu de Québec - Centre hospitalier universitaire de Québec
City
Québec
Country
Canada
Facility Name
CHU Angers
City
Angers
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
Country
France
Facility Name
Institut Bergonie
City
Bordeaux
Country
France
Facility Name
Hopital MORVAN
City
Brest
Country
France
Facility Name
CH René Dubos
City
Cergy Pontoise
Country
France
Facility Name
Hôpital d'Instruction de Armées Percy
City
Clamart
Country
France
Facility Name
Hopital Henri MONDOR
City
Creteil
Country
France
Facility Name
Hôpital Claude Huriez
City
Lille
Country
France
Facility Name
CH Lyon Sud
City
Lyon
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille
Country
France
Facility Name
Hôpital d'Annecy
City
Metz Tessy
Country
France
Facility Name
C.H.U. Brabois
City
Nancy
Country
France
Facility Name
CHU Hoptel dieu
City
Nantes
Country
France
Facility Name
Hôpital l'Archet 1
City
Nice
Country
France
Facility Name
CHU Caremeau
City
Nimes
Country
France
Facility Name
Hopital Saint Louis
City
Paris
Country
France
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
Country
France
Facility Name
Hôpital St Antoine
City
Paris
Country
France
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Facility Name
CHU Rennes - Pontchaillou
City
Rennes
Country
France
Facility Name
Centre René Huguenin
City
Saint Cloud
Country
France
Facility Name
Hôpital Purpan
City
Toulouse
Country
France
Facility Name
CHRU Bretonneau
City
Tours
Country
France
Facility Name
Central Hospital
City
Versailles
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
34195988
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.
Results Reference
derived
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OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy)
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