Chronic myeloid leukemia at diagnosis-chronich phase
Conditions
Interventions
Trade Name: Bosulif (bosutinib)
Pharmaceutical Form: Tablet
Product Name: Pegylated proline-interferon alpha 2b
Product Code: AOP2014
Pharmaceutical Form: Solution for injection in pre-filled pen
Sponsors
St Olavs Hospital -Trondheim University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent form (ICF) before any procedure related to the study 2) Target Population a) Men and women, ages 18 to 75 years b) Newly diagnosed (= 3 months) BCR-ABL positive chronic myeloid leukemia in chronic phase c) Major BCR-ABL transcripts (p210 b2a2(e13a2) and/or b3a2(e14a2)) 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 =65 years) yes F.1.3.1 Number of subjects for this age range 67
Exclusion criteria
Exclusion criteria: 1) Patients with BCR-ABL transcript other than M-BCR-ABL 2) Patients previously treated with tyrosine kinase inhibitors (TKIs). 3) Medical history and concurrent diseases: a) Hypersensitivity to any of the excipients of BOS or RoPegIFN b) Prior treatment with Interferon-a, contraindication to interferon-a, c) Autoimmune disorder, concomitant immunosuppressive treatment or corticosteroids, d) Pre-existing thyroid disease unless controlled with conventional treatment, auto-immune thyroiditis e) Chronic liver disease, f) Prior or ongoing severe psychiatric disease g) HIV positivity, chronic hepatitis B or C h) Uncontrolled or severe cardiac (NYHA Class III or IV) or pulmonary disease, Echocardiography with LVF 2,8 m/s Pulmonary arterial hypertension (PAH), QTc>450 ms (by Barrets correction) i) Other malignant disease during the last 5 years prior to the inclusion except non-melanoma skin carcinoma or carcinoma in situ of the cervix, j) History of significant bleeding disorder unrelated to CML or diagnosed congenital bleeding disorder, k) Subjects with an uncontrolled undercurrent illness or any concurrent condition that, in the investigator’s opinion, would jeopardize the safety of the subject or compliance with the protocol. 4) Prohibited treatments and/or therapies: strong inhibitors/inducers of the CYP 3A4, 5) History / any condition for poor compliance to medical treatment. 6) Women who are pregnant or breastfeeding are not eligible for this study 7) Inability to freely provide consent through judiciary or administrative condition. 8) Ongoing participation to another clinical investigational study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate efficacy of the addition of RoPegIFN to BOS in terms of deep molecular response with the aim of increasing the proportion of patients who may achieve treatment free remission. ;Secondary Objective: •To compare cytogenetic and molecular response including kinetics through the treatment course. •To assess the proportion of patients eligible for randomization after the initial 3 months of BOS. •To determine and to compare safety and tolerability of the treatment in each arm. •To estimate reasons and cumulative rates of RoPegIFN and BOS discontinuation and the median dose of each drug by study arm. •To evaluate the tolerability, of a step-by-step dose schedule for BOS initiation (BOSUSTEP substudy) •To estimate the progression free, event-free and overall survival in each arm. •To estimate the proportion of patients achieving a durable deep molecular response and secondary eligibility for treatment discontinuation. •To compare the measurement of deep molecular response (by standard RTQPCR and digital droplet PCR (ddPCR), •To estimate and compare the rate of successful treatment discontinuation after M48 in each arm ;Primary end point(s): To compare the rate of molecular response 4 (MR4) at 12 months in each treatment arm.;Timepoint(s) of evaluation of this end point: 12 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The rates of molecular responses MR2, MR3, MR4, MR4.5, at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter in each arm. • The cumulative incidence of MR3, MR4, MR4.5 within the same periods in each arm. • The rates of complete cytogenetic response (CCyR) at 3, 6, 12 months. • The rates of undetectable molecular responses for the patients who achieved an MR4 and an MR4.5 in each arm. • The rates of MR4 and MR4.5 by standard RTQPCR IS and digital droplet PCR (ddPCR) on the centralized molecular samples, for the patients who achieve an MR4 or better: comparison for sensitivity and accuracy of the 2 methods at key time points to be decided (ie Month 12 and Month 48) • Time to and duration of CCyR, MR3, MR4, MR4.5. • The proportion of patients eligible for randomization after 3 months of BOS • The rates and characteristics of severe adverse events (SAE) and adverse events (AE) related to BOS and RoPegIFN, from clinical and biological assessments: type and grade according to the NCI CTCAE v4.03. • The dose intensity of RoPegIFN and BOS administered during the first two years of study treatment. The cumulative incidence of discontinuation of the therapies. Reasons of discontinuation. • Other endpoints for the BOSUSTEP substudy within the first three months of BOS: - Any grade of diarrhea and GI toxicity - Other AE > grade 1 related to BOS - The final dose level of BOS by 3 months - The proportion of patients with transient treatment discontinuation - The proportion of patients with permanent treatment discontinuation - Cytogenetic and Molecular responses assessed by BCR-ABL IS at M3 and M6 - The relationship between plasma residual concentration (Cmin) after dose escalation steps and tolerance / efficacy of BOS in a subset of patients (French cohort), and at M3 for Nordic patients who take part in ancillary projects. • The progression free survival, the event-free survival and the overall survival. Occurrence and type o | — |
Countries
Denmark, Finland, France, Norway, Sweden
Contacts
Public ContactHenrik Hjorth-Hansen
St Olavs Hospital
Outcome results
None listed