Chronic Myelogenous LeukaemiaPhase 2BODONCT03205267
Phase II Study Testing the Tolerability and the Efficacy of Bosutinib in Chronic Phase CML Patients
A Phase 2 study testing Bosulif in people with Chronic Myelogenous Leukaemia, run by University of Bonn at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous Leukaemia
- What is being tested?
- Bosulif
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2016to Oct 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Hypersensitivity against Bosutinib or other ingredients of the medicinal product
- Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion
- 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
Show all 26Show fewer
- 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)
- Myocardial infarction within 6 months prior to inclusion
- Unstable angina diagnosed or treated during the past 12 months
- Uncontrolled hypertension, history of labile hypertension
- Known HIV and/or active viral hepatitis (hepatitis B or C). Hepatitis B screening will be performed at screening. Patients with history of hepatitis B with negative HBV DNA may be included when using antiviral prophylaxis
- Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
- Treatment with another investigational product during this study or during the last 30 days prior to study start, except treatment with Interferon alpha within the TIGER (CML V) protocol, which must be stopped at least 7 days prior to study entry
- Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study
- Patient must not have any active bacterial, viral or fungal infection at screening
- Patient must not have severe cerebral dysfunction and/or legal incapacity
- Conditions which interfere with the study treatment at the discretion of the investigator
- Women who are pregnant or breast feeding
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Bonn
Bonn, 53127
Dominik Wolf, Prof. Dr., +49 228 287 17233, dominik.wolf@ukb.uni-bonn.de
About this study
Official title: 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
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.
Read the 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
- Being tested
- Bosulif
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosulifDrug
Also called Bosutinib
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.
| Study group | Role | What they receive |
|---|---|---|
| Bosutinib | Experimental | Drug: Bosulif 100 mg or 500 mg tablets step in dosing scheme Receives: Drug: Bosulif |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Apart from grade 2 to 4 GI toxicity, the occurrence of toxicity will be analyzed in general. This regards all grade toxicity, 2 to 4 grade and 3 to 4 grade toxicity (NCI CTCAE v4.0).
Measured: at month 6, 12 and 24
Molecular response mesured by efficacy parametern
Rating of CCyR, MMR, MR4 and MR4.5 after bone marrow aspiration and biopsy
Measured: at month 3, 6, 12, 18 and 24
Patient-reported outcome measures (QoL)
The EORTC QLQ-CML30 will be scored according to the respective user's guides.
Measured: at month 3 and 6
Progression-free survival (PFS)
Progression will be assessed according to the visit schedule at any visit.
Measured: at month 3, 6, 9, 12, 15, 18, 21 and 24
Overall Survival (OS)
Survival will be assessed according to the visit schedule at any visit.
Measured: at month 3, 6, 9, 12, 15, 18, 21 and 24
The rate of emerging mutations during Bosutinib treatment
The rate and type of mutations will be described. The rate will be given as percentage of patients developing mutations.
Measured: at month 3, 6, 9, 12, 15, 18, 21 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study startMar 2016
- Primary completionOct 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelogenous LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 127 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bonn
- Sponsor type
- University, hospital or other
- Collaborators
- RWTH Aachen University, Ludwig-Maximilians - University of Munich, University of Jena, Heidelberg University, Pfizer
- Responsible party
- Principal investigator, Prof. Dr. Dominik Wolf, University of Bonn
- Investigators
- Dominik GF Wolf, Prof. Dr., Principal investigator, University of Bonn Medical FacultyBrümmendorf H Tim, Prof. Dr., Study chair, University of Aachen Medical Faculty
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03205267
- Sponsor's protocol ID
- MED3-201401-BODO
- Other IDs
- 2014-005531-13, 2014
- Acronym
- BODO
- Status last verified
- Jun 2017
- First submitted
- 29 May 2017
- Last updated
- 2 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03205267
- Acronym / sponsor ID
- BODO / MED3-201401-BODO
- Conditions
- Chronic Myelogenous Leukaemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 127 participants (estimated)
- Lead sponsor
- University of BonnUniversity, hospital or other
- Collaborators
- RWTH Aachen University, Ludwig-Maximilians - University of Munich, University of Jena, Heidelberg University, Pfizer
- Study start
- Mar 2016
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bosutinib | Experimental | Drug: BosulifDrug: Bosulif 100 mg or 500 mg tablets step in dosing scheme |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (26 listed)
- Hypersensitivity against Bosutinib or other ingredients of the medicinal product
- Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosulifAlso: BosutinibPatients 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. | Drug | Bosutinib |
Primary outcome
Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities)
Time frame: within the first 6 months of treatment
calculation of the incidence rate of grade 2 to 4 GI toxicity with and without regard to causality
6 secondary outcomes
overall Tolerability (i.e. all grade, grade 2 to 4 and grade 3 and 4 toxicities)
Time frame: at month 6, 12 and 24
Molecular response mesured by efficacy parametern
Time frame: at month 3, 6, 12, 18 and 24
Patient-reported outcome measures (QoL)
Time frame: at month 3 and 6
Progression-free survival (PFS)
Time frame: at month 3, 6, 9, 12, 15, 18, 21 and 24
Overall Survival (OS)
Time frame: at month 3, 6, 9, 12, 15, 18, 21 and 24
The rate of emerging mutations during Bosutinib treatment
Time frame: at month 3, 6, 9, 12, 15, 18, 21 and 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominik GF Wolf, Prof. Dr. principal investigator
University of Bonn Medical Faculty
Brümmendorf H Tim, Prof. Dr. study chair
University of Aachen Medical Faculty
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosulif in people with Chronic Myelogenous Leukaemia, run by University of Bonn at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dominik GF Wolf, Prof. Dr. (+49 228 287 17233, dominik.wolf@ukb.uni-bonn.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities) (time frame: within the first 6 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.