Clinical trial NCT01872442: Combination of Dasatinib and Peg-Interferon Alpha 2b in First Line for Chronic Myeloid Leukemia in Chronic Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Phase of Chronic Myeloid Leukemia
Lead sponsor: Poitiers University Hospital
Sponsor class: OTHER
First posted: 2013-06-07
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: Interferon alpha was a therapy used in Chronic Myeloid Leukemia in Chronic phase prior to the advent of tyrosine kinase inhibitors. Synergistic effect of the combination of Peg-IFNα2a with Imatinib was demonstrated in the clinical SPIRIT trial. In this study, the investigators address the question of the efficacy and safety of dasatinib in combination with low dose of Peg-IFNα-2b as frontline therapy for patients with newly diagnosed Chronic Myeloid Leukemia in Chronic phase.


Eligibility criteria: Inclusion Criteria:

1. Signed Written Informed Consent.
2. Target Population

   a)18 to 65 years b)Newly diagnosed (≤ 3 months) Philadelphia chromosome positive chronic CP-CML c)Major BCR-ABL transcripts d)Not previously treated for CML except with hydroxyurea or anagrelide e)ECOG Performance Status≤ 2 f)Adequate Organ Function. i)Total bilirubin\< 2.0 times the institutional Upper Limit of Normal ii)Hepatic enzymes(AST, ALT )≤ 2.5 ULN iii)Serum Na, K+, Mg2+ and Ca2+ \> Lower Limit of Normal (LLN) or supplemented iv)Serum Creatinine\< 1.5 ULN g)Women of childbearing potential (WOCBP) must be using an adequate method of contraception.
3. Free subject, without guardianship nor subordination,
4. Health insurance coverage. -

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 :

   1. Hypersensitivity to any of the excipients of dasatinib
   2. Prior treatment with Interferon-α, contraindication to interferon-α, hypersensitivity to any of the excipients of PegIFNα2b,
   3. Concomitant immunosuppressive treatment or corticosteroids,
   4. Preexisting thyroid disease unless it is controlled with conventional treatment, Auto-immune thyroiditis,
   5. Autoimmune disorder, Chronic liver disease,
   6. Prior or ongoing severe psychiatric disease,
   7. Epilepsy or compromised central nervous system(CNS) function,
   8. HIV positivity, chronic hepatitis B or C,
   9. Uncontrolled or significant cardio vascular or pulmonary disease,

   i)Uncontrolled angina, myocardial infarction or congestive heart failure within 6 months, ii)Echocardiography with LVF \< 45% or LLN, peak velocity of tricuspid regurgitant flow \> 2,8 m/s iii)Pulmonary arterial hypertension (PAH), iv)Any history of clinically significant ventricular or supraventricular arrhythmias, v)Diagnosed congenital long QT syndrome, vi)Prolonged QTc interval \> 450 msec (Fredericia) on 3 pre-entry electrocardiogram, vii)Subjects with hypokalemia or hypomagnesemia if it cannot be corrected, j)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, k)History of significant bleeding disorder unrelated to CML, including: i)Diagnosed congenital bleeding disorders (e.g. von Willebrand's disease), ii)Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding. l)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:

   1. strong inhibitors of the CYP3A4,
   2. 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 study.

Primary outcomes:
measure: Cumulative rate of molecular response
timeFrame: at 12 months.
Secondary outcomes:
measure: Rate of complete cytogenetic response
timeFrame: 3, 6, 12, 18, 24 months, and every 12 months thereafter.
measure: Rate of major molecular responses
timeFrame: 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter.
measure: Rate of molecular response
timeFrame: 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter.
measure: Kinetics and duration
timeFrame: 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter
measure: Rate of PegIFN-α2b and dasatinib discontinuation
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Poitiers University Hospital
name: Lydia ROY, MD
role: PRINCIPAL_INVESTIGATOR
References: