Clinical trial NCT03831776: Long-acting Low Dose Ropeginterferon for Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: Bosupeg
Ropeginterferon
Lead sponsor: St. Olavs Hospital
Sponsor class: OTHER
Collaborators: name: Haukeland University Hospital
name: Oslo University Hospital
name: University Hospital of North Norway
name: Helse Stavanger HF
name: Henri Mondor University Hospital
name: Hôpital René Huguenin
name: Hôpital Mignot, Versailles Paris
name: Uppsala University Hospital
name: Odense University Hospital
First posted: 2019-02-06
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Rate of molecular response 4 (MR4)
timeFrame: 12 months
Secondary outcomes:
measure: Rate of molecular response MR2, MR3, MR4, MR4.5 from 1 month up to 24 months and every 6 months thereafter
timeFrame: 2 years
measure: Cumulative incidence of molecular response MR3, MR4, MR4.5
timeFrame: 2 years
measure: Rate of complete cytogenetic response (CCyR) up to 12 months
timeFrame: 12 months
measure: Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5
timeFrame: 2 years
measure: Time to and duration of CCyR, MR3, MR4, MR4.5
timeFrame: 2 years
measure: proportion of patients eligible for randomization after 3 months of Bosutinib
timeFrame: 3 months
measure: rate and characteristics of severe adverse events (SAE)
timeFrame: 2 years
measure: Dose intensity of RoPegIFN and Bosutinib
timeFrame: 2 years
measure: Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation
timeFrame: 2 years
measure: 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)
timeFrame: 6 years
measure: 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)
timeFrame: 6 years
measure: The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48
timeFrame: 4 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg university hospital
city: Aarhus
country: Denmark
facility: Aarhus ...
city: Copenhagen
country: Denmark
facility: Copenhagen ...
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Helsinki
country: Finland
facility: Comprehensive Cancer Center, Hematology
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: Stavanger
country: Norway
facility: Stavanger Universitetssjukehus
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord Norge
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Göteborg
country: Sweden
facility: Göteborg ....
city: Linköping
country: Sweden
facility: Universitetssjukhuset Linköping
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhus
city: Sundsvall
country: Sweden
facility: Sundsvall ...
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: University Hospital
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro
Study officials:
affiliation: St Olavs Hospital, Clinical of Internal Medicine
name: Tom Christian Martinsen, md phd
role: STUDY_DIRECTOR
affiliation: St. Olavs Hospital
name: Henrik Hjorth-Hansen, md phd
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalo-Universitaire Henri Mondor, Service d'Hematologie Clinique
name: Lydia Roy, md phd
role: PRINCIPAL_INVESTIGATOR
References: