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OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy) (OPTIM-DASA)

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ClinicalTrials.gov Identifier: NCT01916785
Recruitment Status : Completed
First Posted : August 6, 2013
Last Update Posted : August 22, 2016
Sponsor:
Collaborators:
Maisonneuve-Rosemont Hospital
University Hospital, Bordeaux
Information provided by (Responsible Party):
Philippe ROUSSELOT, Versailles Hospital

Study Description
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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.


Condition or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia, BCR/ABL Positive Drug: Dasatinib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 289 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2009
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Dasatinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: A1
Arm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake
 Drug: Dasatinib
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
Other Name: Sprycel®
Active Comparator: A2
Arm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake
 Drug: Dasatinib
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
Other Name: Sprycel®
Active Comparator: B
Arm B : Dasatinib standard dose with Cmin < 3nM analysed on blood after 7-10 days dasatinib 100mg intake
 Drug: Dasatinib
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
Other Name: Sprycel®


Outcome Measures
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Primary Outcome Measures :
  1. Cumulative rate of significant AE [ Time Frame: 12 months therapy ]
    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 :
  1. Rate of treatment interruptions [ Time Frame: 12 months therapy ]
    To compare the rate of treatment interruptions

  2. Cumulative duration of dasatinib interruption [ Time Frame: 12 months therapy ]
    To compare the cumulative duration of dasatinib interruption C. To compare the median dose of dasatinib administered during the first 12 months

  3. Mean dose of dasatinib [ Time Frame: 12 months therapy ]
    To compare the mean dose of dasatinib administered during the first 12 months

  4. Cumulative rate of complete cytogenetic response [ Time Frame: 12 months therapy ]
    To compare the cumulative rate of complete cytogenetic response (CCR) at 6, 12 and 18 months, and every 12 months thereafter

  5. Cumulative rate of major molecular response [ Time Frame: 12 months therapy ]
    To compare the cumulative rate of major molecular response (MMR) at 3, 6, 12, and 18 months, and every 6 months thereafter

  6. Median dose of dasatinib administered [ Time Frame: 12 months therapy ]
    To compare the median dose of dasatinib administered during the first 12 months

  7. Cumulative rate of complete molecular response [ Time Frame: 12 months therapy ]
    To compare the cumulative rate of complete molecular response at 3, 6, 12 and 18 months, and every 6 months thereafter

  8. Time to molecular response [ Time Frame: 12 months therapy ]
    To compare the time to molecular response (major or complete)

  9. Relationship between peak plasmatic level and efficacy [ Time Frame: 12 months therapy ]
    To analyse the relationship between peak plasmatic level (Cmax) and efficacy in the three arms

  10. Relationship between through plasmatic level and efficacy [ Time Frame: 12 months therapy ]
    To analyse the relationship between through plasmatic level (Cmin) and efficacy in the three arms

  11. Progression-free survival at 5 years [ Time Frame: 12 months therapy ]
    To compare the progression-free survival (PFS) at 5 years in the three arms

  12. Overall survival at 5 years [ Time Frame: 12 months therapy ]
    To compare the overall survival at 5 years in the three arms

  13. Lymphocyte populations before and during dasatinib therapy [ Time Frame: 12 months therapy ]
    To analyse lymphocyte populations before and during dasatinib therapy (for French participating centers - see appendix 14).

  14. Rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response [ Time Frame: 12 months therapy ]
    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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01916785


Locations
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Sponsors and Collaborators
Versailles Hospital
Maisonneuve-Rosemont Hospital
University Hospital, Bordeaux
Investigators
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Principal Investigator: Philippe ROUSSELOT, Professeur hémato-oncologie Versailles Hospital
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Philippe ROUSSELOT, Clinical Coordinator, Versailles Hospital
ClinicalTrials.gov Identifier: NCT01916785    
Other Study ID Numbers: EudraCT 2008-006854-17
First Posted: August 6, 2013    Key Record Dates
Last Update Posted: August 22, 2016
Last Verified: August 2016
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
 Hematologic Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action