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

NCT03205267 | Unknown Phase 2 DMC

• 2 other identifiers: MED3-201401-BODO2014-005531-13
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myelogenous Leukaemia

Outcome Measures

Primary Outcomes (1)

• Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities)

  calculation of the incidence rate of grade 2 to 4 GI toxicity with and without regard to causality

  within the first 6 months of treatment

Secondary Outcomes (6)

• overall Tolerability (i.e. all grade, grade 2 to 4 and grade 3 and 4 toxicities)

  at month 6, 12 and 24

• Molecular response mesured by efficacy parametern

  at month 3, 6, 12, 18 and 24

• Patient-reported outcome measures (QoL)

  at month 3 and 6

• Progression-free survival (PFS)

  at month 3, 6, 9, 12, 15, 18, 21 and 24

• Overall Survival (OS)

  at month 3, 6, 9, 12, 15, 18, 21 and 24

Other Outcomes (6)

• Vascular biology substudy: analysis of clinical and laboratory vascular and metabolic risk factors

  baseline, at months 6, 12 and 24

• Pharmacokinetic (PK), pharmacodynamic (PD) substudy

  at day 1, months 1, 2, 3, 12, 18, 24

• Telomere substudy

  at months 1, 2, 3, 12 and 24

Study Arms (1)

Bosutinib

EXPERIMENTAL

Drug: Bosulif 100 mg or 500 mg tablets step in dosing scheme

Drug: Bosulif

Interventions

Bosulif DRUG

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.

Also known as: Bosutinib

Bosutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female patients aged ≥18 years
• ECOG performance status of 0 to 2
• CML in 1st or late chronic phase
• Intolerant or resistant to pretreatment with one of the approved 1st line TKIs (Imatinib, Nilotinib or Dasatinib). Imatinib therapy prior to 2nd generation TKI therapy for a maximum of 6 weeks is allowed.
• Patients must have a serum creatinine of ≤ 2 x ULN, SGOT/SGPT ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (except known Gilbert's syndrome), and Lipase ≤ 1.5 x ULN
• Female patients of childbearing potential must have a negative pregnancy test performed during screening period
• Male and female patients of reproductive potential must currently use a highly effective contraceptive method and be willing to keep on using it throughout the study and for 6 months following discontinuation of study drug.

You may not qualify if:

• Hypersensitivity against Bosutinib or other ingredients of the medicinal product
• Patients with BCR-ABL negative CML
• Patients having received Imatinib for more than 6 weeks prior to initiation of 2nd generation TKI (either Nilotinib or Dasatinib)
• Patients with known T315I or V299L mutation
• Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4
• History of pancreatitis, inflammatory bowel disease requiring systemic or topical immunosuppressive therapy within the last 12 months
• Impaired cardiac function, including any of the following:
• History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG
• ST depression of \>1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG
• Congenital long QT syndrome
• QTc\> 450 msec in the screening ECG
• QT-prolonging concomitant medication
• History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG
• History of or presence of clinically significant resting bradycardia (\< 50 beats per minute)
• Unstable angina diagnosed or treated during the past 12 months

Sponsors & Collaborators

• University of Bonn: lead
• RWTH Aachen University: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• University of Jena: collaborator
• Heidelberg University: collaborator
• Pfizer: collaborator

Study Sites (1)

University Hospital Bonn

Bonn, 53127, Germany

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dominik GF Wolf, Prof. Dr.

  University of Bonn Medical Faculty

  PRINCIPAL INVESTIGATOR

• Brümmendorf H Tim, Prof. Dr.

  University of Aachen Medical Faculty

  STUDY CHAIR

Central Study Contacts

Dominik GF Wolf, Prof. Dr.

CONTACT

+49 228 287 17233; dominik.wolf@ukb.uni-bonn.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Prof. Dr. med. D. Wolf

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: July 2, 2017
• Study Start: March 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: July 2, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)