- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03831776
Long-acting Low Dose Ropeginterferon for Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis (BosuPeg)
April 18, 2023 updated by: St. Olavs Hospital
A Study of Efficacy and Safety of Long-acting Low Dose Ropeginterferon in Patients With Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis: a Randomized Prospective Trial
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)
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
212
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Henrik Hjorth-Hansen, md phd
- Phone Number: 0047 73598673
- Email: henrik.hjorth-hansen@ntnu.no
Study Contact Backup
- Name: Lydia Roy, md phd
- Phone Number: 0033 0149812111
Study Locations
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Aalborg, Denmark
- Not yet recruiting
- Aalborg University Hospital
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Contact:
- Rie Sander Bech
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Aarhus, Denmark
- Not yet recruiting
- Aarhus ...
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Contact:
- Jesper Stentoft
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Copenhagen, Denmark
- Not yet recruiting
- Copenhagen ...
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Contact:
- Christen Lykkegård Andersen
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Odense, Denmark
- Not yet recruiting
- Odense Universitetshospital
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Contact:
- Andreja Dimitrijevic
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Contact:
- Marianne Augustenborg
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Helsinki, Finland
- Not yet recruiting
- Comprehensive Cancer Center, Hematology
-
Contact:
- Perttu M Koskenvesa
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-
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Bergen, Norway
- Recruiting
- Haukeland Universitetssjukehus
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Contact:
- Bjørn Tore Gjertsen
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Contact:
- Øystein Sefland
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Oslo, Norway
- Recruiting
- Oslo Universitetssykehus
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Contact:
- Kristin H Låstad
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Sub-Investigator:
- Eivind Galteland
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Sub-Investigator:
- Tobias Gedde-Dahl
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Stavanger, Norway
- Recruiting
- Stavanger Universitetssjukehus
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Contact:
- Margrete Friestad
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Principal Investigator:
- Mohammed Waleed Majeed
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Tromsø, Norway
- Recruiting
- Universitetssykehuset Nord Norge
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Contact:
- Mats I Olsen
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Contact:
- Anders Vik
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Trondheim, Norway
- Recruiting
- St Olavs Hospital
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Contact:
- Henrik Hjorth-Hansen, md phd
- Email: henrik.hjorth-hansen@ntnu.no
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Göteborg, Sweden
- Not yet recruiting
- Göteborg ....
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Linköping, Sweden
- Not yet recruiting
- Universitetssjukhuset Linköping
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Contact:
- Kourosh Lotfi
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Contact:
- Arta Dreimane
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Lund, Sweden
- Not yet recruiting
- Skane University Hospital
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Contact:
- Johan Richter
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Contact:
- Anna Lubking
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Stockholm, Sweden
- Not yet recruiting
- Karolinska Universitetssjukhus
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Contact:
- Leif Stenke
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Sundsvall, Sweden
- Not yet recruiting
- Sundsvall ...
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Contact:
- Anders Själander
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Umeå, Sweden
- Not yet recruiting
- Norrlands universitetssjukhus
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Contact:
- Berit Markevärn
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Uppsala, Sweden
- Not yet recruiting
- University Hospital
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Contact:
- Ulla Olsson-Strömberg
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Örebro, Sweden
- Not yet recruiting
- Universitetssjukhuset Örebro
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Contact:
- Erik Ahlstrand
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bosutinib-Ropeginterferon combination
|
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.
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.
Other Names:
|
Active Comparator: Bosutinib monotherapy
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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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of molecular response 4 (MR4)
Time Frame: 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)
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12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of molecular response MR2, MR3, MR4, MR4.5 from 1 month up to 24 months and every 6 months thereafter
Time Frame: 2 years
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2 years
|
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Cumulative incidence of molecular response MR3, MR4, MR4.5
Time Frame: 2 years
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2 years
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Rate of complete cytogenetic response (CCyR) up to 12 months
Time Frame: 12 months
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12 months
|
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Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5
Time Frame: 2 years
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2 years
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Time to and duration of CCyR, MR3, MR4, MR4.5
Time Frame: 2 years
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2 years
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proportion of patients eligible for randomization after 3 months of Bosutinib
Time Frame: 3 months
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3 months
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rate and characteristics of severe adverse events (SAE)
Time Frame: 2 years
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type and grade according to the NCI CTCAE v4.03
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2 years
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Dose intensity of RoPegIFN and Bosutinib
Time Frame: 2 years
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2 years
|
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Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation
Time Frame: 2 years
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2 years
|
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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)
Time Frame: 6 years
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6 years
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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)
Time Frame: 6 years
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6 years
|
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The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48
Time Frame: 4 years
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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
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4 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Tom Christian Martinsen, md phd, St Olavs Hospital, Clinical of Internal Medicine
- Principal Investigator: Henrik Hjorth-Hansen, md phd, St. Olavs Hospital
- Principal Investigator: Lydia Roy, md phd, Centre Hospitalo-Universitaire Henri Mondor, Service d'Hematologie Clinique
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 25, 2019
Primary Completion (Anticipated)
February 1, 2024
Study Completion (Anticipated)
March 1, 2028
Study Registration Dates
First Submitted
February 4, 2019
First Submitted That Met QC Criteria
February 4, 2019
First Posted (Actual)
February 6, 2019
Study Record Updates
Last Update Posted (Actual)
April 19, 2023
Last Update Submitted That Met QC Criteria
April 18, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BosuPeg TRIAL
- 2018-001044-54 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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