A phase II study to assess the efficacy and safety of frontline combination of dasatinib (SPRYCEL®) and pegylated-interferon alpha 2b (Peg-IFNa2b) therapy in patients newly diagnosed with chronic phase chronic myeloid leukaemia (CP-CML) - DASA-PEGIF

• Conditions: Patients with newly diagnosed chronic phase Chronic Myeloid Leukemia (CP-CML), not previously treated with Tyrosine Kinase Inhibitors (TKIs). First line therapy.; MedDRA version: 14.1Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-003389-42-FR
• Lead Sponsor: CHU DE POITIERS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-21
• Last Update Posted: 26 August 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 < 2.0 times the institutional Upper Limit of Normal (ULN)
ii)Hepatic enzymes (AST, ALT ) = 2.5 times the institutional ULN
iii)Serum Na, K+, Mg2+, Phosphate and Ca2+ > Lower Limit of Normal (LLN)
iv)Serum Creatinine < 1.5 time the institutional ULN
g)Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
•Amenorrhea that has lasted for ? 12 consecutive months without another cause, or
•For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where their partner is sterile (e.g. vasectomy) should be considered to be of childbearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product.
A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study to minimize the risk of pregnancy.
3)Expected compliance to the treatment.
4) Health insurance coverage.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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 <45% or LLN,
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 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified