Long-acting Low Dose Ropeginterferon for Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis

NCT ID: NCT03831776

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-25
• Study Completion Date: 2024-12-31

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)

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bosutinib-Ropeginterferon combination

Group Type: EXPERIMENTAL

Bosutinib

Intervention Type: DRUG

Bosutinib, provided by Pfizer, starting dose of 200mg QD and stepwise dose escalation (\> 300 mg/d \> 400 mg/d) during the first three months. A pharmacological study will be performed in the French cohort (BOSUSTEP Substudy). BOS residual plasma concentration (Cmin) will be checked after initiation, before each dose step in the French cohort, and at M3 also for Nordic patients in ancillary studies.

Ropeginterferon

Intervention Type: DRUG

Ro-Peg-Interferon α2b will be supplied by AOP Orphan to be administered by subcutaneous injections from prefilled injection pens. RoPegIFN will be given in an open-label fashion. Patients assigned to RoPegIFN will start with 50 μg injected subcutaneously every 14 days, in combination with Bosutinib.

Bosutinib monotherapy

Group Type: ACTIVE_COMPARATOR

Bosutinib

Intervention Type: DRUG

Bosutinib, provided by Pfizer, starting dose of 200mg QD and stepwise dose escalation (\> 300 mg/d \> 400 mg/d) during the first three months. A pharmacological study will be performed in the French cohort (BOSUSTEP Substudy). BOS residual plasma concentration (Cmin) will be checked after initiation, before each dose step in the French cohort, and at M3 also for Nordic patients in ancillary studies.

Interventions

Bosutinib

Bosutinib, provided by Pfizer, starting dose of 200mg QD and stepwise dose escalation (\> 300 mg/d \> 400 mg/d) during the first three months. A pharmacological study will be performed in the French cohort (BOSUSTEP Substudy). BOS residual plasma concentration (Cmin) will be checked after initiation, before each dose step in the French cohort, and at M3 also for Nordic patients in ancillary studies.

Intervention Type: DRUG

Ropeginterferon

Ro-Peg-Interferon α2b will be supplied by AOP Orphan to be administered by subcutaneous injections from prefilled injection pens. RoPegIFN will be given in an open-label fashion. Patients assigned to RoPegIFN will start with 50 μg injected subcutaneously every 14 days, in combination with Bosutinib.

Intervention Type: DRUG

Other Intervention Names

RoPegIFN

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role: collaborator

Henri Mondor University Hospital

OTHER

Sponsor Role: collaborator

Hôpital René Huguenin

UNKNOWN

Sponsor Role: collaborator

Hôpital Mignot, Versailles Paris

UNKNOWN

Sponsor Role: collaborator

Uppsala University Hospital

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tom Christian Martinsen, md phd

Role: STUDY_DIRECTOR

St Olavs Hospital, Clinical of Internal Medicine

Henrik Hjorth-Hansen, md phd

Role: PRINCIPAL_INVESTIGATOR

St. Olavs Hospital

Lydia Roy, md phd

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalo-Universitaire Henri Mondor, Service d'Hematologie Clinique

Locations

Aalborg university hospital

Aalborg, , Denmark

Aarhus ...

Aarhus, , Denmark

Copenhagen ...

Copenhagen, , Denmark

Odense Universitetshospital

Odense, , Denmark

Comprehensive Cancer Center, Hematology

Helsinki, , Finland

Haukeland Universitetssjukehus

Bergen, , Norway

Oslo Universitetssykehus

Oslo, , Norway

Stavanger Universitetssjukehus

Stavanger, , Norway

Universitetssykehuset Nord Norge

Tromsø, , Norway

St Olavs Hospital

Trondheim, , Norway

Göteborg ....

Gothenburg, , Sweden

Universitetssjukhuset Linköping

Linköping, , Sweden

Skåne University Hospital

Lund, , Sweden

Universitetssjukhuset Örebro

Örebro, , Sweden

Karolinska Universitetssjukhus

Stockholm, , Sweden

Sundsvall ...

Sundsvall, , Sweden

Norrlands Universitetssjukhus

Umeå, , Sweden

University Hospital

Uppsala, , Sweden

Countries

Denmark; Finland; Norway; Sweden

Other Identifiers

2018-001044-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BosuPeg TRIAL

Identifier Type: -

Identifier Source: org_study_id