A Multicenter Phase 3 Randomized, Open-Label Study of Bosutinib versus Imatinib in Adult Patients with Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

Phase 1

• Conditions: Chronic Myeloid Leukemia (CML); MedDRA version: 20.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005101-31-NL
• Lead Sponsor: Pfizer Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-06-20
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 536

Inclusion Criteria

Main Inclusion Criteria:
1. Molecular diagnosis of CP CML of = 6 months (from initial diagnosis).
• Diagnosis of CP CML with molecular confirmation by detection of BCR-ABL rearrangement at screening (cytogenetic assessment for Philadelphia chromosome is not required for enrollment); diagnosis of CP CML will be defined as all of the following per ELN criteria:
(a) <15% blasts in peripheral blood and bone marrow;
(b) <30% blasts plus promyelocytes in peripheral blood and bone marrow;
(c) <20% basophils in peripheral blood;
(d) =100 x 109/L platelets (=100,000/mm3);
(e) No evidence of extramedullary disease except hepatosplenomegaly; AND
(f) No prior diagnosis of AP or BP CML.
• Philadelphia chromosome status will be identified at screening. Both Philadelphia positive (Ph+) and Philadelphia negative (Ph-) patients may be included.
2. Adequate hepatic, renal and pancreatic function defined as:
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) =2.5 x upper limit of normal (ULN) or =5 x ULN if attributable to liver involvement of leukemia.
• Total bilirubin =2.0 x ULN (unless associated with Gilbert’s syndrome).
• Creatinine =1.5 x ULN.
3. Ability to take oral tablets.
4. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
5. Age = 18 years.
6. Negative serum pregnancy test within 2 weeks of the first dose of study drug if the patient is a woman of childbearing potential. A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Patients and patient's partners of childbearing potential (physically able to have children) and who are sexually active must agree to use double barrier contraception, oral contraceptives, intra-uterine device, intra-muscular contraceptive, vasectomy/surgical sterilization, true abstinence or other approved method of birth control consistently and correctly during the study and for at least 28 days after they have stopped taking the study drug.
7. Ability to provide written informed consent prior to any study related screening procedures being performed.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 420
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105

Exclusion Criteria

Main Exclusion Criteria:
1. Any prior medical treatment for CML including tyrosine kinase inhibitors (TKIs) with the exception of hydroxyurea and/or anagrelide treatment which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject’s region.
2. Any past or current CNS involvement, including leptomeningeal leukemia.
3. Hypersensitivity to the active substance or to any of the following excipients: Microcrystalline cellulose (E460), croscarmellose sodium (E468), poloxamer 188, povidone (E1201), magnesium stearate (E470b), polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, Talc (E553b), iron oxide yellow (E172).
4. Extramedullary disease only.
5. Major surgery or radiotherapy within 14 days of randomization.
6. Concomitant use of or need for medications known to prolong the QT interval.
7. History of clinically significant or uncontrolled cardiac disease, including:
• History of, or active, congestive heart failure.
• Uncontrolled angina or hypertension within 3 months.
• Myocardial infarction (within 12 months).
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Diagnosed or suspected congenital or acquired prolonged QT history or prolonged QTc. (QTcF should not exceed 500 msec).
• Unexplained syncope.
8.Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included.
9. Recent or ongoing clinically significant gastrointestinal (GI) disorder e.g. Crohn's Disease, Ulcerative Colitis or prior total or partial gastrectomy.
10. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least 12 months.
11. Uncontrolled hypomagnesemia or uncorrected hypokalemia, due to potential effects on the QT interval.
12. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.
13. Women who are pregnant, planning to become pregnant during the study or are breastfeeding a child, or men who are planning to father a child during their participation in this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified