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

NCT03831776 | Completed Phase 2 DMC

• 2 other identifiers: BosuPeg TRIAL2018-001044-54
• Study Type: interventional
• Target: 212
• Locations: 4 countries
• Sites: 18

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

Keywords

Bosupeg; Ropeginterferon

Outcome Measures

Primary Outcomes (1)

• Rate of molecular response 4 (MR4)

  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)

  12 months

Secondary Outcomes (12)

• 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

Study Arms (2)

Bosutinib-Ropeginterferon combination

EXPERIMENTAL

Drug: Bosutinib; Drug: Ropeginterferon

Bosutinib monotherapy

ACTIVE COMPARATOR

Drug: Bosutinib

Interventions

Bosutinib 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.

Bosutinib monotherapy; Bosutinib-Ropeginterferon combination

Ropeginterferon 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.

Also known as: RoPegIFN

Bosutinib-Ropeginterferon combination

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• St. Olavs Hospital: lead
• Haukeland University Hospital: collaborator
• Oslo University Hospital: collaborator
• University Hospital of North Norway: collaborator
• Helse Stavanger HF: collaborator
• Henri Mondor University Hospital: collaborator
• Hôpital René Huguenin: collaborator
• Hôpital Mignot, Versailles Paris: collaborator
• Uppsala University Hospital: collaborator
• Odense University Hospital: collaborator

Study Sites (18)

Aalborg university hospital

Aalborg, Denmark

Location

Aarhus ...

Aarhus, Denmark

Location

Copenhagen ...

Copenhagen, Denmark

Location

Odense Universitetshospital

Odense, Denmark

Location

Comprehensive Cancer Center, Hematology

Helsinki, Finland

Location

Haukeland Universitetssjukehus

Bergen, Norway

Location

Oslo Universitetssykehus

Oslo, Norway

Location

Stavanger Universitetssjukehus

Stavanger, Norway

Location

Universitetssykehuset Nord Norge

Tromsø, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

Göteborg ....

Gothenburg, Sweden

Location

Universitetssjukhuset Linköping

Linköping, Sweden

Location

Skåne University Hospital

Lund, Sweden

Location

Universitetssjukhuset Örebro

Örebro, Sweden

Location

Karolinska Universitetssjukhus

Stockholm, Sweden

Location

Sundsvall ...

Sundsvall, Sweden

Location

Norrlands Universitetssjukhus

Umeå, Sweden

Location

University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tom Christian Martinsen, md phd

  St Olavs Hospital, Clinical of Internal Medicine

  STUDY DIRECTOR

• Henrik Hjorth-Hansen, md phd

  St. Olavs Hospital

  PRINCIPAL INVESTIGATOR

• Lydia Roy, md phd

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 6, 2019
• Study Start: March 25, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 8, 2025

Record last verified: 2025-06

Locations

NO (5); FI (1); SE (8); DK (4)