BOSUTINIB for Chronic myeloid leukemia

Inclusion criteria

• {"criterion_text":"- 1) Signed written informed consent form (ICF) before any procedure related to the study\n- 2) Target Population a) Men and women, ages 18 to 75 years\n- 2) Target Population b) Newly diagnosed (≤ 3 months) BCR-ABL positive chronic myeloid leukemia in chronic phase\n- 2) Target Population c) Major BCR-ABL transcripts (p210 b2a2(e13a2) and/or b3a2 (e14a2))\n- 2) Target Population d) Not previously treated for CML except with hydroxyurea or anagrelide\n- 2) Target Population e) ECOG Performance Status (ECOG PS) ≤ 2\n- 2) Target Population f) Adequate organ function.\n- 2) Target Population f) i. Total bilirubin < 1,5 times the institutional Upper Limit of Normal (ULN)\n- 2) Target Population f) ii. Hepatic enzymes ASAT and ALAT < 2 times the institutional ULN\n- 2) Target Population f) iii. Serum Creatinine < 1.5 time the institutional ULN\n- 2) Target Population f) iv. Lipase < 1.5 time the institutional ULN\n- 3) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. See section 9.2.2 “Pregnancy”.\n- 4) WOCBP must have a negative serum or urine pregnancy test at screening.\n- 5) Free subject, without guardianship nor subordination\n- 6) Health insurance coverage\n- Eligibility criteria for randomization at 3 months: 1) Complete hematologic response achieved at M3\n- Eligibility criteria for randomization at 3 months: 2) At least able to tolerate BOS 300mg daily\n- Eligibility criteria for randomization at 3 months: 3) Platelet >75x109 /L and ANC>1 x109 /L\n- Eligibility criteria for randomization at 3 months: 4) ASAT and ALAT< 3 ULN (< Grade 2)\n- Eligibility criteria for randomization at 3 months: 5) Still fulfill other original inclusion and exclusion criteria,\n- Eligibility criteria for randomization at 3 months: 6) HADS depression and anxiety scores <11 each: otherwise psychiatrist approval required for RoPegIFN Non-eligible pts may continue on BOS single drug, at investigator’s discretion."}

Exclusion criteria

• {"criterion_text":"- 1) Patients with BCR-ABL transcript other than M-BCR-ABL\n- 2) Patients previously treated with tyrosine kinase inhibitors (TKIs).\n- 3) Inability to freely provide consent through judiciary or administrative condition.\n- 4) Ongoing participation to another clinical investigational study.\n- 5) Medical history and concurrent diseases: a) Hypersensitivity to any of the excipients of BOS or RoPegIFN\n- 5) Medical history and concurrent diseases: b) Prior treatment with Interferon-α, contraindication to interferon-α,\n- 5) Medical history and concurrent diseases: c) Autoimmune disorder, concomitant immunosuppressive treatment or corticosteroids,\n- 5) Medical history and concurrent diseases: d) Pre-existing thyroid disease unless controlled with conventional treatment, autoimmune thyroiditis\n- 5) Medical history and concurrent diseases: e) Chronic liver disease,\n- 5) Medical history and concurrent diseases: f) Prior or ongoing severe psychiatric disease\n- 5) Medical history and concurrent diseases: g) HIV positivity, chronic hepatitis B or C\n- 5) Medical history and concurrent diseases: 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)\n- 5) Medical history and concurrent diseases: i) Other malignant disease during the last 5 years prior to the inclusion except nonmelanoma skin carcinoma or carcinoma in situ of the cervix,\n- 5) Medical history and concurrent diseases: j) History of significant bleeding disorder unrelated to CML or diagnosed congenital bleeding disorder,\n- 5) Medical history and concurrent diseases: k) 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.\n- 6) Prohibited treatments and/or therapies: strong inhibitors/inducers of the CYP 3A4,\n- 7) History / any condition for poor compliance to medical treatment.\n- 8) Women who are pregnant or breastfeeding are not eligible for this study"}

Primary endpoints

• {"endpoint_text":"- To compare the rate of molecular response 4 (MR4 ) at 12 months in each treatment arm.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- The rates of molecular responses MR2 , MR3 , MR4 , MR4.5, at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter in each arm.","definition_or_measurement_approach":"Measured as rates of molecular responses (MR2, MR3, MR4, MR4.5) at specified timepoints."}
• {"endpoint_text":"- The cumulative incidence of MR3 , MR4 , MR4.5 within the same periods in each arm","definition_or_measurement_approach":"Cumulative incidence of molecular responses (MR3, MR4, MR4.5) at listed time periods."}
• {"endpoint_text":"- The rates of complete cytogenetic response (CCyR) at 3, 6, 12 months.","definition_or_measurement_approach":"Rates of CCyR measured at months 3, 6, 12."}
• {"endpoint_text":"- The rates of undetectable molecular responses for the patients who achieved an MR4 and an MR4.5 in each arm.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to and duration of CCyR, MR2 , MR3 , MR4 ,MR4.5 .","definition_or_measurement_approach":""}
• {"endpoint_text":"- The proportion of patients eligible for randomization after 3 months of BOS","definition_or_measurement_approach":"Proportion eligible for randomization after 3 months of bosutinib treatment."}
• {"endpoint_text":"- The rates and characteristics of severe adverse events (SAE) and adverse events (AE) related to BOS and RoPegIFN, from clinical and biological assessments: type and grade according to the NCI CTCAE v4.03.","definition_or_measurement_approach":"Adverse events assessed by clinical and biological assessments; type and grade per NCI CTCAE v4.03."}
• {"endpoint_text":"- The dose intensity of RoPegIFN and BOS administered during the first two years of study treatment. The cumulative incidence of discontinuation of the therapies. Reasons of discontinuation.","definition_or_measurement_approach":"Dose intensity over first two years; cumulative incidence and reasons for discontinuation."}
• {"endpoint_text":"- Other endpoints for the BosuPeg substudy: -Biomarkers of response, failure and toxicity. A) Fraction and phenotype of leukemic cells in the stem cell and progenitor cell compartment at debut and 3 and 12 months of treatment. B)Phenotype and function of immune cells at debut and 3 and 12 months of treatment. C)Non-CR-ABL mutations at debut and during treatment D)TCR clonality at debut and during treatment E)Changes in plasma cytokine profile during treatment","definition_or_measurement_approach":"Exploratory biomarker assessments (cell fractions/phenotype, immune function, non-CR-ABL mutations, TCR clonality, plasma cytokine profiles) at baseline, 3 and 12 months."}
• {"endpoint_text":"- Other endpoints for the BosuPeg substudy: - Identification of novel potential targets for therapy of CML","definition_or_measurement_approach":""}
• {"endpoint_text":"- The progression free survival, the event-free survival and the overall survival. Occurrence and type of BCR-ABL TK mutation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Quality of life assessment by QLQC30 and CML24 questionnaires at key time point (Day 1, M3, M6, M12, M24, at planned BOS-discontinuation, 6 and 24 months post discontinuation as well as at restart after discontinuation and 6 months after restart).","definition_or_measurement_approach":"Quality of life measured using QLQ-C30 and CML24 questionnaires at listed timepoints."}
• {"endpoint_text":"- The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48–60 after minimally 2 years in continuous MR4 or better","definition_or_measurement_approach":""}
• {"endpoint_text":"- The proportion of patients in treatment free remission after 6, 12, 24 and 36 months of BOS discontinuation.","definition_or_measurement_approach":""}

Other endpoints

• {"endpoint_text":"- Other endpoints for the BosuPeg substudy: -Biomarkers of response, failure and toxicity. A) Fraction and phenotype of leukemic cells in the stem cell and progenitor cell compartment at debut and 3 and 12 months of treatment. B)Phenotype and function of immune cells at debut and 3 and 12 months of treatment. C)Non-CR-ABL mutations at debut and during treatment D)TCR clonality at debut and during treatment E)Changes in plasma cytokine profile during treatment","definition_or_measurement_approach":"Exploratory biomarker analyses as specified (phenotype/function of leukemic and immune cells, mutation profiling, TCR clonality, cytokines) at baseline, 3 and 12 months."}
• {"endpoint_text":"- Other endpoints for the BosuPeg substudy: - Identification of novel potential targets for therapy of CML","definition_or_measurement_approach":""}

Denmark

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

28-11-2024

Processing Time Days

28

Number Of Sites

7

Number Of Participants

34

Sweden

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

29-11-2024

Processing Time Days

29

Number Of Sites

7

Number Of Participants

55

Norway

Earliest CTIS Part Ii Submission Date

21-11-2024

Latest Decision Or Authorization Date

28-11-2024

Processing Time Days

7

Number Of Sites

4

Number Of Participants

64

Finland

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

29-11-2024

Processing Time Days

29

Number Of Sites

1

Number Of Participants

11

Primary sponsor

Full Name

St. Olavs Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway