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

Primary Purpose

Chronic Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bosutinib
Ropeginterferon
Sponsored by
St. Olavs Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Bosupeg, Ropeginterferon

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Aalborg university hospital
  • Aarhus ...
  • Copenhagen ...
  • Odense Universitetshospital
  • Comprehensive Cancer Center, Hematology
  • Haukeland UniversitetssjukehusRecruiting
  • Oslo UniversitetssykehusRecruiting
  • Stavanger UniversitetssjukehusRecruiting
  • Universitetssykehuset Nord NorgeRecruiting
  • St Olavs HospitalRecruiting
  • Göteborg ....
  • Universitetssjukhuset Linköping
  • Skåne University Hospital
  • Karolinska Universitetssjukhus
  • Sundsvall ...
  • Norrlands Universitetssjukhus
  • University Hospital
  • Universitetssjukhuset Örebro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bosutinib-Ropeginterferon combination

Bosutinib monotherapy

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Rate of molecular response MR2, MR3, MR4, MR4.5 from 1 month up to 24 months and every 6 months thereafter
Cumulative incidence of molecular response MR3, MR4, MR4.5
Rate of complete cytogenetic response (CCyR) up to 12 months
Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5
Time to and duration of CCyR, MR3, MR4, MR4.5
proportion of patients eligible for randomization after 3 months of Bosutinib
rate and characteristics of severe adverse events (SAE)
type and grade according to the NCI CTCAE v4.03
Dose intensity of RoPegIFN and Bosutinib
Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation
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)
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)
The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48
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

Full Information

First Posted
February 4, 2019
Last Updated
April 18, 2023
Sponsor
St. Olavs Hospital
Collaborators
Haukeland University Hospital, Oslo University Hospital, University Hospital of North Norway, Helse Stavanger HF, Henri Mondor University Hospital, Hôpital René Huguenin, Hôpital Mignot, Versailles Paris, Uppsala University Hospital, Odense University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03831776
Brief Title
Long-acting Low Dose Ropeginterferon for Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis
Acronym
BosuPeg
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 25, 2019 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
March 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Olavs Hospital
Collaborators
Haukeland University Hospital, Oslo University Hospital, University Hospital of North Norway, Helse Stavanger HF, Henri Mondor University Hospital, Hôpital René Huguenin, Hôpital Mignot, Versailles Paris, Uppsala University Hospital, Odense University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
Bosupeg, Ropeginterferon

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
212 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bosutinib-Ropeginterferon combination
Arm Type
Experimental
Arm Title
Bosutinib monotherapy
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Bosutinib
Intervention Description
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
Intervention Name(s)
Ropeginterferon
Other Intervention Name(s)
RoPegIFN
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of molecular response 4 (MR4)
Description
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)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
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
Title
Cumulative incidence of molecular response MR3, MR4, MR4.5
Time Frame
2 years
Title
Rate of complete cytogenetic response (CCyR) up to 12 months
Time Frame
12 months
Title
Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5
Time Frame
2 years
Title
Time to and duration of CCyR, MR3, MR4, MR4.5
Time Frame
2 years
Title
proportion of patients eligible for randomization after 3 months of Bosutinib
Time Frame
3 months
Title
rate and characteristics of severe adverse events (SAE)
Description
type and grade according to the NCI CTCAE v4.03
Time Frame
2 years
Title
Dose intensity of RoPegIFN and Bosutinib
Time Frame
2 years
Title
Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation
Time Frame
2 years
Title
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
Title
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
Title
The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48
Description
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
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henrik Hjorth-Hansen, md phd
Phone
0047 73598673
Email
henrik.hjorth-hansen@ntnu.no
First Name & Middle Initial & Last Name or Official Title & Degree
Lydia Roy, md phd
Phone
0033 0149812111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tom Christian Martinsen, md phd
Organizational Affiliation
St Olavs Hospital, Clinical of Internal Medicine
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Henrik Hjorth-Hansen, md phd
Organizational Affiliation
St. Olavs Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lydia Roy, md phd
Organizational Affiliation
Centre Hospitalo-Universitaire Henri Mondor, Service d'Hematologie Clinique
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg university hospital
City
Aalborg
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rie Sander Bech
Facility Name
Aarhus ...
City
Aarhus
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesper Stentoft
Facility Name
Copenhagen ...
City
Copenhagen
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christen Lykkegård Andersen
Facility Name
Odense Universitetshospital
City
Odense
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreja Dimitrijevic
First Name & Middle Initial & Last Name & Degree
Marianne Augustenborg
Facility Name
Comprehensive Cancer Center, Hematology
City
Helsinki
Country
Finland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Perttu M Koskenvesa
Facility Name
Haukeland Universitetssjukehus
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bjørn Tore Gjertsen
First Name & Middle Initial & Last Name & Degree
Øystein Sefland
Facility Name
Oslo Universitetssykehus
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristin H Låstad
First Name & Middle Initial & Last Name & Degree
Eivind Galteland
First Name & Middle Initial & Last Name & Degree
Tobias Gedde-Dahl
Facility Name
Stavanger Universitetssjukehus
City
Stavanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margrete Friestad
First Name & Middle Initial & Last Name & Degree
Mohammed Waleed Majeed
Facility Name
Universitetssykehuset Nord Norge
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mats I Olsen
First Name & Middle Initial & Last Name & Degree
Anders Vik
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik Hjorth-Hansen, md phd
Email
henrik.hjorth-hansen@ntnu.no
Facility Name
Göteborg ....
City
Göteborg
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Name
Universitetssjukhuset Linköping
City
Linköping
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kourosh Lotfi
First Name & Middle Initial & Last Name & Degree
Arta Dreimane
Facility Name
Skåne University Hospital
City
Lund
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Richter
First Name & Middle Initial & Last Name & Degree
Anna Lubking
Facility Name
Karolinska Universitetssjukhus
City
Stockholm
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leif Stenke
Facility Name
Sundsvall ...
City
Sundsvall
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anders Själander
Facility Name
Norrlands Universitetssjukhus
City
Umeå
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Berit Markevärn
Facility Name
University Hospital
City
Uppsala
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulla Olsson-Strömberg
Facility Name
Universitetssjukhuset Örebro
City
Örebro
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik Ahlstrand

12. IPD Sharing Statement

Learn more about this trial

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

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