Primary: To compare the Major Molecular Response (MMR) rate at 24 weeks of ABL001 versus bosutinibSecondary: To compare additional parameters of the efficacy of ABL001 versus bosutinib. Safety, tolerability.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
MMR rate at week 24.
Secondary outcome
MMR rate at week 96. Cytogenic response (incl. time to, duration). MMR rate at
all time points (except week 24 and 96). Time to MMR, duration of MMR. Time to
treatment failure. Progression free survival. Overall survival. Adverse events.
Background summary
ABL001 is an agent intended to be evaluated for the treatment of patients with
Chronic Myelogenous Leukemia (CML). In the ongoing study study, ABL001 was
found to produce clinically meaningful and durable responses in patients who
have had treatment failure after a minimum of 2 prior ATP-binding site Tyrosin
kinase inhibitors (TKIs), with an acceptable safety and tolerability profile.
The purpose of this pivotal study is to compare the efficacy of ABL001 with
that of bosutinib in the treatment of patients with CML in a chronic phase
(CML-CP) having previously been treated with a minimum of two prior ATP-binding
site TKIs with BCR-ABL1 ratios >= 0,1% IS at screening.
Study objective
Primary:
To compare the Major Molecular Response (MMR) rate at 24 weeks of ABL001 versus
bosutinib
Secondary:
To compare additional parameters of the efficacy of ABL001 versus bosutinib.
Safety, tolerability.
Study design
Multicenter phase 3 open-label randomized study. Randomization (2:1) to
• ABL001 40 mg b.i.d.
• Bosutinib 500 mg QD.
Treatment up to 96 weeks after the last subject received the first study dose.
Follow-up for survival.
222 subjects.
Patient failing treatment with bosutinib are being offered the possibility to
receive ABL001 as studytreatment
Intervention
Treatment with ABL001 or bosutinib
Study burden and risks
Risk: Adverse effects of ABL001 or bosutinib.
Burden: screening, max. approx. 51 visits on treatment, follow-up for survival
(every 12 weeks).
Physical examination: every visit until end of treatment.
Blood tests (35 mL/occasion): every visit until end of treatment. Additional
samples for PK (18-28 mL extra) and biomarkers (216 mL extra).
Bone marrow punction: 6 times (plus 2 times biopsy).
ECG: 7 times.
Echocardiography: 3 times.
Pulmonary function test: 3 times.
Questionnaires: approx. 8 times (symptoms, impact on quality of life, impact on
work productivity, change in condition).
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Male or female patients with a diagnosis of CML-CP >= 18 years of age.
2. Laboratory values at screening visit: see protocol page 36.
3. BCR-ABL1 ratio >= 0,1% IS according to central laboratory at the screening
examination for patients intolerant to the most recent TKI therapy
4. Prior treatment with a minimum of 2 prior ATP-binding site TKIs (i.e.
imatinib, nilotinib, dasatinib, radotinib or ponatinib).
5. Failure or intolerance to the last previous TKI therapy at the time of
screening. See protocol page 36-37 for details.
6. ECOG performance status 0-1-2
Exclusion criteria
1. Known presence of the T315I or V299L mutation at any time prior to study
entry.
2. Known second chronic phase of CML after previous progression to AP/BC.
3. Previous treatment with a hematopoietic stem-cell transplantation.
4. Cardiac or cardiac repolarization abnormality. See protocol page 38 for
details.
5. History of acute pancreatitis within 1 year of study entry or past medical
history of chronic pancreatitis.
6. Pregnancy, lactation, insufficient contraception for females of childbearing
potential .
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002461-66-NL |
| ClinicalTrials.gov | NCT03106779 |
| CCMO | NL62672.029.17 |