NCT03205267

Phase II Study Testing the Tolerability and the Efficacy of Bosutinib in Chronic Phase CML Patients

Multicenter, Open-label Single Arm Phase II Study Testing the Tolerability and the Efficacy of Bosutinib step-in Dosing in Chronic Phase CML Patients Intolerant or Refractory to Previous Imatinib, Nilotinib or Dasatinib Therapy

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 127 (estimated)
• Sponsor: University of Bonn · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Bosutinib is a 2nd generation tyrosine kinase inhibitor that has shown promising results from first up to fourth line treatment in patients with in chronic phase of chronic myelogenous leukaemia. Most patients discontinuing the treatment with Bosutinib do so because of side effects occuring early after starting the treatment. A step in dosing scheme could improve these early toxicities. The aim of this study therefore is to demonstrate that temporary lowering of the Bosutinib dose during early treatment may help to reduce or prevent side effects while preserving efficacy.

Detailed description

Objectives: The objective of the BODO trial is to assess the tolerability and efficacy of a step-in dosing concept of the dual SRC-ABL kinase inhibitor Bosutinib in CP-CML patients who either developed intolerance or treatment failure to previous Imatinib, Dasatinib or Nilotinib as 1st line therapy. Primary endpoint: • Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities) within the first 6 months of treatment Secondary endpoints: * Tolerability (i.e. all grade, grade 2 to 4 and grade 3 and 4 toxicities) at month 6, 12 and 24 * Efficacy parameters: CCyR, MMR, MR4 and MR4.5 rate at month 3, 6, 12, 18 and 24 * Patient-reported outcome measures (QoL) * Progression-free survival (PFS) * Overall survival (OS) * The rate of emerging mutations during Bosutinib treatment Exploratory endpoints linked to substudies: Vascular biology substudy: * Effects of previous therapy on the baseline vascular risk profile (i.e. Nilotinib- vs. Dasatinib-pre-treatment) * Biological and clinical surrogates for vascular alterations during Bosutinib therapy at baseline, months 6, 12, and 24 Pharmacokinetic (PK), pharmacodynamic (PD) and immunology sub- study: * Correlation of PK with response and toxicity * Correlation of PK with PD (i.e. phosphoproteomic changes) in immune cell populations * Correlation of PD changes in immune cell populations with response * Evaluation of the effects of Bosutinib on frequency and phenotype of immune cells * Evaluation whether Bosutinib-induced changes of immune cells correlate to response Ultra-deep next-generation sequencing (UD-NGS) and telomere substudy: * Documentation of subclone evolution or elimination during Bosutinib treatment * Evaluation of telomere length in leukemic and non-leukemic cells as a prognostic indicator for depth and kinetics of response to and tolerability of Bosutinib

Conditions

• Chronic Myelogenous Leukaemia

Interventions

Type	Name	Description
DRUG	Bosulif	Patients will start with dose-level 1 (300 mg once daily) Bosutinib. If patients do not experience any toxicity or only G1 toxicity, they will be dose-increased first to dose-level 2 (400 mg once daily ) and then to dose-level 3 (500 mg once daily). Dose will not be escalated above 500 mg which is the dose recommended by the summary of product information. If patients experience G2 toxicity, the study drug will be further continued at the same dose-level. In patients with G3 or G4 toxicities, therapy will be withheld until toxicity resolved to \<G2.

Timeline

• Start date: 2016-03-01
• Primary completion: 2019-10-01
• Completion: 2019-10-01
• First posted: 2017-07-02
• Last updated: 2017-07-02

Locations

1 site across 1 country: Germany