A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
|ClinicalTrials.gov Identifier: NCT02130557|
Recruitment Status : Active, not recruiting
First Posted : May 5, 2014
Last Update Posted : February 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive||Drug: Bosutinib Drug: Imatinib||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||535 participants|
|Masking:||None (Open Label)|
|Masking Description:||NOTE: Value was Open Label in old format; This study has an open-label design. Although most efficacy studies have a double blind design, this is not feasible in this trial, due to the complexity of the dose reduction and dose escalation schemes with tablets of various sizes, dosage strengths, as well as the number of tablets that would be required daily. However, the opportunity for bias is mitigated by the use of objective outcome measures (MMR, CCyR, CHR). The Investigators will be instructed to ensure that laboratory/pathology personnel are blinded to treatment information. For these reasons, an open-label, randomized study is appropriate.|
|Official Title:||A Multicenter Phase 3 Randomized, Open-label Study Of Bosutinib Versus Imatinib In Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia|
|Actual Study Start Date :||July 2014|
|Primary Completion Date :||August 2016|
|Estimated Study Completion Date :||August 2020|
Bosutinib, 400 mg, oral administration once a day
Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy. This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.
Active Comparator: Imatinib
Imatinib, 400 mg, oral administration once a day
Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial.
Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.
- The proportion of participants with Major Molecular Response (MMR) at 12 Months in the bosutinib arm with that of the imatinib arm [ Time Frame: 12 Months ]MMR is defined as <0.1%Bcr-Abl1 on the International Scale (IS) by Real Time Quantitative Polymerase Chain Reaction (RT-PCR)
- The proportion of participants with MMR by 18 Months in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 18 Months ]For the analysis of MMR by 18 months a patient is counted as a response if MMR occurs at or before the 18 months, even if MMR is subsequently lost at or before the 18 months. A patient never achieving MMR at or before 18 months is deemed a non-response.
- The duration of MMR in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 5 Years ]Duration of MMR is measured only for participants who initially respond to study medication.
- The proportion of participants with Complete Cytogenetic Response (CCyR) by 12 Months in both treatment groups [ Time Frame: 12 Months ]CCyR is defined as absence of detectable Ph chromosomes in bone marrow aspirate
- The duration of CCyR in both treatment groups [ Time Frame: 5 Years ]Duration of response is measured only for participants who initially respond to study medication.
- The event free survival (EFS) in both treatment groups. [ Time Frame: 5 Years ]
Event free survival (EFS) defined as the time without occurrence of:
- Death due to any cause.
- Transformation to AP or BP at any time.
Loss of CHR.
- Loss of CHR is defined as the appearance of any of the following, confirmed by a second determination ≥4 weeks later (unless associated with CML-related treatment discontinuation):
- WBC count that rises to >20.0 x 109/L.
- Platelet count that rises to ≥600 x 109/L.
- Appearance of palpable spleen or other extramedullary involvement proven by biopsy.
- Appearance of 5% myelocytes in the peripheral blood.
- Appearance of blasts or promyelocytes in the peripheral blood.
- The overall survival (OS) in both treatment groups. [ Time Frame: 5 years ]Overall survival (OS), defined as the time from randomization to the occurrence of death due to any cause.
- The population pharmacokinetics (PK) and correlations between trough concentrations of bosutinib and key efficacy and safety parameters.of bosutinib administered once daily. [ Time Frame: 84 Days ]The objectives of the population PK analysis are 1) to develop a population PK model which describes the PK of bosutinib in this patient population, 2) to evaluate the influence of demographic and clinical covariates on the exposure of bosutinib, 3) to explore the relationship between trough concentrations of bosutinib with clinical safety (drug related adverse effects such as GI AEs, and any other major AEs) and efficacy endpoints.
- The safety profile of bosutinib and imatinib treatments. [ Time Frame: 5 years ]Safety will be assessed on an ongoing basis by physical examination including measurement of vital signs, laboratory assessments, standard safety evaluations (electrocardiograms [ECGs] for monitoring of QTc interval changes and echocardiograms/MUGA scans for monitoring ventricular function) and recording of adverse events (AEs) and serious adverse events (SAEs). Adverse events will be graded according to the NCI CTC version 4. Discontinuations due to AEs will be considered the main comparative safety endpoint for AEs. In addition standard laboratory assessments will be performed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02130557
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|Study Director:||Pfizer CT.gov Call Center||Pfizer|