Patients with newly diagnosed chronic phase Chronic Myeloid Leukemia (CP-CML), not previously treated with Tyrosine Kinase Inhibitors (TKIs). First line therapy. MedDRA version: 14.1 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SPRYCEL® 100mg
Pharmaceutical Form: Tablet
Trade Name: VIRAFERONPEG®, 50 µg
Pharmaceutical Form: Powder and solvent for solution for injection
Sponsors
CHU DE POITIERS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Principal inclusion criteria 1) Signed Written Informed Consent: All patients must have read and sign the informed consent form (ICF) before any procedure related to the study, registration/inclusion in the study. 2) Target Population a) Men and women, ages 18 to 69 years b) Newly diagnosed (= 3 months) Philadelphia chromosome positive chronic phase chronic myeloid leukemia (CP-CML) c) Major BCR-ABL transcripts (p210 b2a2 or b3a2) d) Not previously treated for CML except with hydroxyurea or anagrelide e) ECOG Performance Status (ECOG PS) = 2 f) Adequate Organ Function. i) Total bilirubin Lower Limit of Normal (LLN) iv) Serum Creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1) Patients with BCR-ABL other than M-BCR-ABL, Philadelphia negative CML. 2) Patients previously treated with Tyrosine Kinase Inhibitors (TKIs). 3) Medical history and concurrent diseases: a) Prior treatment with Interferon-a / Contraindication to interferon-a, b) Concomitant immunosuppressive treatment or corticosteroids, c) Preexisting thyroid disease unless it is controlled with conventional treatment, Auto-immune thyroiditis, d) Autoimmune disorder, Chronic liver disease, e) Prior or ongoing severe psychiatric disease, f) Epilepsy or compromised central nervous system(CNS) function, g) HIV positivity, chronic hepatitis B or C, h) Uncontrolled or significant cardio vascular disease, i) Uncontrolled angina, congestive heart failure or MI within 6 months, ii) Echocardiography with LVF 450 msec (Fredericia) on 3 pre-entry electrocardiogram, vii) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib, i) Other malignant disease during the last 5 years prior to the inclusion except basal cell carcinoma of the skin or carcinoma in situ of the cervix, j) History of significant bleeding disorder unrelated to CML, including: i) Diagnosed congenital bleeding disorders (e.g. von Willebrand’s disease), ii) Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VIII antibodies), iii) Ongoing or recent (? 3 months) significant gastrointestinal bleeding. k) Another severe or life –threatening medical disease. 4) Women who are pregnant or breastfeeding, WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug. 5) Prohibited treatments and/or therapies: a) strong inhibitors of the CYP 3A4, b) category I drugs that are generally accepted to have a risk of causing “Torsades de Pointes”. Patients must discontinue the drug minimum 7 days prior to starting dasatinib. 6) History /any condition for poor compliance to the treatment. 7) Inability to freely provide consent through judiciary or administrative condition. 8) Ongoing participation to another clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy of dasatinib combined to Peg-interferon-a2b on the cumulative rate of molecular response 4.5 (MR4.5) at 12 months, as frontline therapy for newly diagnosed CP-CML patients.;Secondary Objective: •To assess the rates of complete cytogenetic response (CCgR) at 3, 6, 12, 18, 24 months, and every 12 months thereafter. •To assess the rates of major molecular responses (MMR) at 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. •To assess the rate of molecular response 4.5 (MR4.5) at 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. •To assess the rates of molecular responses 5.0 (MR5.0) at 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter, for the patients who achieved MR4.5. •To estimate the cumulative rates of CCR, MMR, MR4.5, MR5.0 within the same periods. •Kinetics and duration of CCR, MMR, MR4.5MR5.0. •To determine the safety and tolerability of the combination of PegIFN-a2b and dasatinib. •To estimate the rate of PegIFN-a2b and dasatinib discontinuation, and dose reduction. •To analyse the residual plasmatic levels (Cmin) of dasatinib. •To estimate the progression free survival, event-free and overall survival. .;Primary end point(s): The primary endpoint is the cumulative rate of molecular responses 4.5 (MR4.5) achieved at 12 months. Centralized analyses of molecular response by RTQPCR will be performed for all molecular assessments in this study. Molecular response 4.5 (MR4.5) is defined by either a positive BCR-ABL/ABL ratio =0.0032 on the international scale or by undetectable BCR-ABL with the analysis of at least 32000 copies of ABL (according to the ELN recommendations by N. Cross et al., leukemia 2012[26]). ;Timepoint(s) of evaluation of this end point: 12 months since enrolment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The rates of complete cytogenetic response (CCgR) at 3, 6, 12, 18, 24 months and every 12 months thereafter. • The rates of major molecular responses (MMR) at 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. • The rate of molecular response 4.5 (MR4.5) at 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. • The rates of the molecular responses 5.0 (MR5.0) at 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter, for the patients who achieved MR4.5. • The cumulative rates of CCR, MMR, MR4.5, MR5.0 within the same periods. • Time to and duration of CCR, MMR, MR4.5MR5.0. • Incidence and characteristics of severe adverse events (SAE) and adverse events (AE) related to the therapy, from clinical and biological assessments: type and grade according to the NCI CTCAE v4.0. • The cumulative incidence of discontinuation for PegIFN-a2b or dasatinib during the first two years of study treatment. Time to and duration of discontinuation • The dose intensity of PegIFN-a2b and dasatinib administered during the first two years of study treatment. • The relationship between residual (Cmin) plasmatic levels and SAE related to dasatinib at M1, M6. • The progression free survival, the event-free survival and the overall survival. • Quality of life questionnaire (EORTC QLQ-C30) with PegIFN-a2b and dasatinib at Day 1, M3, M6, M12 and at the end of the study. ;Timepoint(s) of evaluation of this end point: 12 months since enrolment | — |
Countries
France
Contacts
Public ContactFanny ABRIAT
CHU DE POITIERS
Outcome results
None listed