Long-acting Low Dose Ropeginterferon for Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis
- Conditions
- Chronic Myeloid Leukemia
- Interventions
- Drug: Ropeginterferon
- Registration Number
- NCT03831776
- Lead Sponsor
- St. Olavs Hospital
- Brief Summary
To study the efficacy and safety of combination of Ro-Peg-interferon-α2b (RoPegIFN) with Bosutinib (BOS) in comparison to BOS monotherapy, as frontline therapy for newly diagnosed chronic myeloid leukemia patients, and 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. (NCMLSG study #NordCML012)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 212
- Signed written informed consent form (ICF) before any procedure related to the study
- Newly diagnosed (≤ 3 months) BCR-ABL positive chronic myeloid leukemia (CML) in chronic phase
- Major BCR-ABL transcripts (p210 b2a2(e13a2) and/or b3a2 (e14a2)
- Not previously treated for CML except with hydroxyurea or anagrelide
- ECOG Performance Status (ECOG PS) ≤ 2
- Adequate organ function: Total bilirubin < 1,5 times the institutional Upper Limit of Normal (ULN); Hepatic enzymes ASAT and ALAT < 2 times the institutional ULN; Serum Creatinine < 1.5 time the institutional ULN; Lipase < 1.5 time the institutional ULN
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study.
- WOCBP must have a negative serum or urine pregnancy test at screening.
- Free subject, without guardianship nor subordination
- Health insurance coverage
- Patients with BCR-ABL transcript other than M-BCR-ABL
- Patients previously treated with tyrosine kinase inhibitors (TKIs).
- Inability to freely provide consent through judiciary or administrative condition.
- Ongoing participation to another clinical investigational study.
- Medical history and concurrent diseases: a) Hypersensitivity to any of the excipients of BOS or RoPegIFN, b) Prior treatment with Interferon-α, contraindication to interferon-α, 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 < 45% or LLN, peak velocity of tricuspid regurgitant flow > 2,8 m/s, pulmonary arterial hypertension (PAH), QTc>450 ms (by Barrets correction)
- Other malignant disease during the last 5 years prior to the inclusion except non-melanoma skin carcinoma or carcinoma in situ of the cervix,
- History of significant bleeding disorder unrelated to CML or diagnosed congenital bleeding disorder,
- 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.
- Prohibited treatments and/or therapies: strong inhibitors/inducers of the CYP 3A4,
- History / any condition for poor compliance to medical treatment.
- Women who are pregnant or breastfeeding are not eligible for this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bosutinib-Ropeginterferon combination Ropeginterferon - Bosutinib-Ropeginterferon combination Bosutinib - Bosutinib monotherapy Bosutinib -
- Primary Outcome Measures
Name Time Method Rate of molecular response 4 (MR4) 12 months Molecular response 4 (MR4) is defined by either a positive BCR-ABL/ABL ratio ≤ 0.01% on the international scale (IS) or by undetectable BCR-ABL with the analysis of at least 10000 copies of ABL or 24000 copies of GUS (according to the ELN recommendations by N. Cross et al., Leukemia 2015)
- Secondary Outcome Measures
Name Time Method Dose intensity of RoPegIFN and Bosutinib 2 years Rate of molecular response MR2, MR3, MR4, MR4.5 from 1 month up to 24 months and every 6 months thereafter 2 years Cumulative incidence of molecular response MR3, MR4, MR4.5 2 years Rate of complete cytogenetic response (CCyR) up to 12 months 12 months Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5 2 years Time to and duration of CCyR, MR3, MR4, MR4.5 2 years proportion of patients eligible for randomization after 3 months of Bosutinib 3 months rate and characteristics of severe adverse events (SAE) 2 years type and grade according to the NCI CTCAE v4.03
Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation 2 years Quality of life assessment by QLQC30 questionnaire up to 6 years at key time point (Day 1, month 3, month 6, month 12, month 24, month 48, month 54, month 72) 6 years Quality of life assessment by CML24 questionnaire up to 6 years at key time point (Day 1, month 3, month 6, month 12, month 24, month 48, month 54, month 72) 6 years The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48 4 years Sustained deep molecular response (MR) criteria will be defined according updated data and ELN guidelines before the first patient will achieve month 48 (at least a MR4 over a 12 months period and confirmed on the last centralized measurement at month 48
Trial Locations
- Locations (18)
Aarhus ...
🇩🇰Aarhus, Denmark
Göteborg ....
🇸🇪Göteborg, Sweden
Universitetssjukhuset Linköping
🇸🇪Linköping, Sweden
Sundsvall ...
🇸🇪Sundsvall, Sweden
Aalborg university hospital
🇩🇰Aalborg, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
Copenhagen ...
🇩🇰Copenhagen, Denmark
Skåne University Hospital
🇸🇪Lund, Sweden
Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Karolinska Universitetssjukhus
🇸🇪Stockholm, Sweden
University Hospital
🇸🇪Uppsala, Sweden
Haukeland Universitetssjukehus
🇳🇴Bergen, Norway
Oslo Universitetssykehus
🇳🇴Oslo, Norway
St Olavs Hospital
🇳🇴Trondheim, Norway
Universitetssykehuset Nord Norge
🇳🇴Tromsø, Norway
Comprehensive Cancer Center, Hematology
🇫🇮Helsinki, Finland
Stavanger Universitetssjukehus
🇳🇴Stavanger, Norway
Universitetssjukhuset Örebro
🇸🇪Örebro, Sweden