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

August 19, 2016 updated by: Philippe ROUSSELOT, Versailles Hospital

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).

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

289

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Calgary, Canada
        • Southern Alberta Cancer Research Institute
      • Greenfield Park, Canada
        • Hopital Charles LeMoyne
      • Halifax, Canada
        • Queen elisabeth II Health Sciences Center
      • Lachenaie, Canada
        • CH Pierre LeGardeur
      • Moncton, Canada
        • Moncton City Hospital
      • Montréal, Canada
        • Hôpital Général Juif - Sir. Mortimer B. Davis
      • Montréal, Canada
        • Hôpital Maisonneuve-Rosemont
      • Montréal, Canada
        • Hôpital Royal Victoria
      • Québec, Canada
        • Hôpital de l'Enfant Jésus - Centre hospitalier affilié universitaire de Québec
      • Québec, Canada
        • Pavillon Hôtel-Dieu de Québec - Centre hospitalier universitaire de Québec
  • France
      • Angers, France
        • Chu Angers
      • Bobigny, France
        • Hopital Avicenne
      • Bordeaux, France
        • Institut Bergonie
      • Brest, France
        • Hopital Morvan
      • Cergy Pontoise, France
        • CH René Dubos
      • Clamart, France
        • Hôpital d'Instruction de Armées Percy
      • Creteil, France
        • Hôpital Henri Mondor
      • Lille, France
        • Hôpital Claude Huriez
      • Lyon, France
        • CH Lyon Sud
      • Marseille, France
        • Institut Paoli-Calmettes
      • Metz Tessy, France
        • Hopital d'Annecy
      • Nancy, France
        • C.H.U. Brabois
      • Nantes, France
        • CHU Hoptel dieu
      • Nice, France
        • Hôpital l'Archet 1
      • Nimes, France
        • CHU Caremeau
      • Paris, France
        • Hopital Saint Louis
      • Paris, France
        • Hôpital Necker-Enfants Malades
      • Paris, France
        • Hopital St Antoine
      • Poitiers, France
        • CHU Poitiers
      • Rennes, France
        • CHU Rennes - Pontchaillou
      • Saint Cloud, France
        • Centre Rene Huguenin
      • Toulouse, France
        • Hopital Purpan
      • Tours, France
        • CHRU Bretonneau
      • Versailles, France
        • Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • Sprycel®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 months therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of treatment interruptions
Time Frame: 12 months therapy
To compare the rate of treatment interruptions
12 months therapy
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
12 months therapy
Mean dose of dasatinib
Time Frame: 12 months therapy
To compare the mean dose of dasatinib administered during the first 12 months
12 months therapy
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
12 months therapy
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
12 months therapy
Median dose of dasatinib administered
Time Frame: 12 months therapy
To compare the median dose of dasatinib administered during the first 12 months
12 months therapy
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
12 months therapy
Time to molecular response
Time Frame: 12 months therapy
To compare the time to molecular response (major or complete)
12 months therapy
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
12 months therapy
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
12 months therapy
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 months therapy
Overall survival at 5 years
Time Frame: 12 months therapy
To compare the overall survival at 5 years in the three arms
12 months therapy
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).
12 months therapy
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)
12 months therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Versailles Hospital

Collaborators

University Hospital, Bordeaux
Maisonneuve-Rosemont Hospital

Investigators

  • Principal Investigator: Philippe ROUSSELOT, Professeur hémato-oncologie, Versailles Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

December 18, 2012

First Submitted That Met QC Criteria

August 2, 2013

First Posted (Estimate)

August 6, 2013

Study Record Updates

Last Update Posted (Estimate)

August 22, 2016

Last Update Submitted That Met QC Criteria

August 19, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT 2008-006854-17

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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