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

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ClinicalTrials.gov Identifier: NCT03831776
Recruitment Status : Recruiting
First Posted : February 6, 2019
Last Update Posted : April 5, 2022
Sponsor:
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
Information provided by (Responsible Party):
St. Olavs Hospital

Study Description
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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)

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Bosutinib Drug: Ropeginterferon Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 25, 2019
Estimated Primary Completion Date : March 15, 2023
Estimated Study Completion Date : March 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Bosutinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Bosutinib-Ropeginterferon combination Drug: 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.

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.
Other Name: RoPegIFN
Active Comparator: Bosutinib monotherapy Drug: 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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 ]
  2. Cumulative incidence of molecular response MR3, MR4, MR4.5 [ Time Frame: 2 years ]
  3. Rate of complete cytogenetic response (CCyR) up to 12 months [ Time Frame: 12 months ]
  4. Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5 [ Time Frame: 2 years ]
  5. Time to and duration of CCyR, MR3, MR4, MR4.5 [ Time Frame: 2 years ]
  6. proportion of patients eligible for randomization after 3 months of Bosutinib [ Time Frame: 3 months ]
  7. rate and characteristics of severe adverse events (SAE) [ Time Frame: 2 years ]
    type and grade according to the NCI CTCAE v4.03

  8. Dose intensity of RoPegIFN and Bosutinib [ Time Frame: 2 years ]
  9. Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation [ Time Frame: 2 years ]
  10. 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 ]
  11. 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 ]
  12. The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48 [ Time Frame: 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03831776


Contacts
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Contact: Henrik Hjorth-Hansen, md phd 0047 73598673 henrik.hjorth-hansen@ntnu.no
Contact: Lydia Roy, md phd 0033 0149812111

Locations
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Sponsors and Collaborators
St. Olavs Hospital
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
Investigators
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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
More Information
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Responsible Party: St. Olavs Hospital
ClinicalTrials.gov Identifier: NCT03831776    
Other Study ID Numbers: BosuPeg TRIAL
2018-001044-54 ( EudraCT Number )
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: April 5, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Olavs Hospital:
Bosupeg
Ropeginterferon
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
 Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases