Study comparing ABL001 with Bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP)

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Romania, Russian Federation, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
EUCTR2016-002461-66 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
A phase 3, multi-center, open-label, randomized study of oral asciminib versus bosutinib in patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors. (BASEC)

Wissenschaftlicher Titel
A phase 3, multi-center, open-label, randomized study of oral ABL001 versus bosutinib in patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (ICTRP)

Öffentlicher Titel
A Phase 3 study comparing treatment of patients with Chronic Myelogenous Leukemia with ABL001 versus Bosutinib (ICTRP)

Untersuchte Krankheit(en)
Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors
MedDRA version: 20.0Level: LLTClassification code 10009012Term: Chronic myelogenous leukemiaSystem Organ Class: 100000004864;Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Untersuchte Intervention

Product Code: ABL001
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: asciminib
Current Sponsor code: ABL001
Other descriptive name: ABL001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20 -

Trade Name: Bosulif
Product Name: Bosutinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BOSUTINIB
CAS Number: 380843-75-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100 -

Product Code: ABL001
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: asciminib
Current Sponsor code: ABL001
Other descriptive name: ABL001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Bosulif
Product Name: Bosutinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BOSUTINIB
CAS Number: 380843-75-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

(ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

Inclusion criteria:
1. Male or female patients with a diagnosis of CML-CP = 18 years of age
2. Patients must meet all of the following laboratory values at the screening visit:
- < 15% blasts in peripheral blood and bone marrow
- < 30% blasts plus promyelocytes in peripheral blood and bone marrow
- < 20% basophils in the peripheral blood
- = 50 x 109/L (= 50,000/mm3) platelets
- Transient prior therapy related thrombocytopenia (< 50,000/mm3 for = 30 days prior to screening) is acceptable
- No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
3. BCR-ABL ratio = 1% IS according to central laboratory at the screening examination
4. Prior treatment with a minimum of 2 prior ATP-binding site TKIs (i.e. imatinib, nilotinib, dasatinib, radotinib or ponatinib)
5. Failure or intolerance to the last previous TKI therapy at the time of screening (adapted from the 2013 ELN Guidelines Bacarrani 2013)
- Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as follows. Patients must meet at least 1 of the following criteria.
Three months after the initiation of therapy: No CHR or > 95% Ph+ metaphases
Six months after the initiation of therapy: BCR-ABL ratio > 10% IS and/or > 65% Ph+ metaphases
Twelve months after initiation of therapy: BCR-ABL ratio > 10% IS and/or > 35% Ph+ metaphases
At any time after the initiation of therapy, loss of CHR, CCyR or PCyR
At any time after the initiation of therapy, the development of new BCR-ABL mutations
At any time after the initiation of therapy, confirmed loss of MMR in 2 consecutive tests, of which one must have a BCR-ABL ratio = 1% IS
At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+
- Intolerance is defined as:
Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
7. Adequate end organ function as defined by (as per central laboratory tests):
- Total bilirubin = 1.5 x ULN except for patients with Gilbert?s syndrome who may only be included if total bilirubin = 3.0 x ULN or direct bilirubin = 1.5 x ULN
- Aspartate transaminase (AST) = 3.0 x ULN
- Alanine transaminase (ALT) = 3.0 x ULN
- Serum amylase = ULN
- Serum lipase = ULN
- Alkaline phosphatase = 2.5 x ULN
- Creatinine clearance = 50 mL/min as calculated using Cockcroft-Gault formula
8. Patients must avoid consumption of grapefruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications. Orange
juice is allowed.
9. Written informed consent obtained prior to any screening procedures.
10. Patients must have the following electrolyte values within normal limits (as per central laboratory tests) or corrected to be within normal limits with supplements prior to first dose of study medication:
- Potassium
- Magnesium
- Total calcium (c (ICTRP)

Exclusion criteria:
1. Known presence of the T315I or V299L mutation at any time prior to study entry
2. Known second chronic phase of CML after previous progression to AP/BC
3. Previous treatment with a hematopoietic stem-cell transplantation
4. Patient planning to undergo allogeneic hematopoietic stem cell transplantation
5. Cardiac or cardiac repolarization abnormality, including any of the following:
- History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- QTcF at screening =450 ms (male patients), =460 ms (female patients)
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
Inability to determine the QTcF interval
6. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, pulmonary
hypertension)
7. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
8. History of elevation in amylase or lipase (> ULN) within 1 year other than that which may have occurred with gallstones, trauma, or medical procedures
9. History of acute or chronic liver disease
10. Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
11. History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
12. Known history of Human Immunodeficiency Virus (HIV), chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBcAb / anti HBc) will be performed at screening
13. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
14. Treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with study treatment
- Moderate or strong inducers of CYP3A
- Moderate or strong inhibitors of CYP3A and/or P-gp
- Substrates of CYP3A4/5, CYP2C8, or CYP2C9 with narrow therapeutic index
15. Previous treatment with or known/ suspected hypersensitivity to ABL001 or any of its excipients
16. Previous treatment with or known/ suspected hypersensitivity to bosutinib or any of its excipients
17. Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
18. Pregnant

Primäre und sekundäre Endpunkte
Main Objective: To compare the MMR rate at 24 weeks of ABL001 versus bosutinib;Secondary Objective: To compare additional parameters of the efficacy of ABL001 versus bosutinib;Primary end point(s): Major Molecular Response (MMR) rate at 24 weeks;Timepoint(s) of evaluation of this end point: 24 weeks (ICTRP)

Secondary end point(s): MMR rate at 96 weeks;Timepoint(s) of evaluation of this end point: 96 weeks (ICTRP)

Registrierungsdatum
07.07.2017 (ICTRP)

Einschluss des ersten Teilnehmers
09.10.2017 (ICTRP)

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Public Information Desk, infoph.hungary@novartis.com, 00 36 1 457-6500, Novartis Hungary Kft. (ICTRP)

Sekundäre IDs
CABL001A2301 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002461-66 (ICTRP)