This study has been transitioned to CTIS with ID 2024-510947-71-00 check the CTIS register for the current data. Primary:To assess the tolerability of asciminib versus nilotinib with respect to the time to discontinuation of study treatment due to…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to discontinuation of study treatment due to adverse event.
Secondary outcome
Discontinuation due to lack of efficacy, treatment failure, disease
progression, suboptimal response, death.
Patient-reported disease-related symptoms, functioning, and health-related
quality of life.
Adverse events.
Background summary
Considerable advancements in treatment of patients with CML-CP have increased
the life expectancy of patients making it a chronic disease requiring long term
medication. This emphasizes the need for treatments that combine high efficacy
with a favorable safety profile as improving over the currently available
options. There remains an unmet medical need for newly diagnosed patients with
CML-CP requiring chronic treatment and for a specific targeted treatment option
that is highly efficacious while minimizing adverse events.
To assess if asciminib may address these needs, the ongoing Phase III study
CABL001J12301 sets out to evaluate primarily the efficacy of asciminib in newly
diagnosed Chronic Myelogenous Leukemia (CML) patients.
The primary purpose of this Phase IIIb study is to focus on the patient
relevant outcomes and to assess the tolerability of asciminib, as it translates
in study treatment discontinuations due to adverse events, in comparison with
that of the second generation Tyrosine Kinase Inhibitor nilotinib, in adult
patients with newly diagnosed Ph+ CML-CP. The study also aims to assess
treatment impact on quality of life. Generating such data is patient relevant
as well as deemed important for Health Technology Assessment bodies* decision
making.
Study objective
This study has been transitioned to CTIS with ID 2024-510947-71-00 check the CTIS register for the current data.
Primary:
To assess the tolerability of asciminib versus nilotinib with respect to the
time to discontinuation of study treatment due to adverse event.
Secondary:
• Efficacy of asciminib versus nilotinib in terms of discontinuation due to
lack of efficacy/treatment failure/disease progression/suboptimal
response/death.
• Effect of asciminib versus nilotinib on patient-reported disease-related
symptoms, functioning, and health-related quality of life.
• Safety and tolerability profile of asciminib versus nilotinib during the
course of study.
Study design
This is a phase IIIb, multi-center, open-label, randomized study of oral
asciminib 80 mg QD versus nilotinib 300 mg BID in adult patients with newly
diagnosed Ph+ CML-CP. It is planned to randomize approximately 541 patients in
the study in a 1:1 randomization to asciminib or nilotinib. Randomization will
be stratified based on European Treatment Outcome Study (EUTOS) long-term
survival (ELTS) score (low versus intermediate versus high) to help achieve a
balance between the treatment arms.
The primary purpose of this study is to assess the tolerability of asciminib in
comparison with that of nilotinib. Study duration approximately 4.5-5 years.
Approximate treatment duration for an individual participant is expected to be
between 2 to 4.5 years dependent on when the patient enrolls in the study.
Visits are planned every 2 weeks for the first month of treatment and every 12
weeks until end of treatment.
Intervention
Participants will be assigned at Day 1 to one of the following 2 treatment arms
in a ratio of 1:1:
Arm 1: Asciminib tablets 80 mg QD administered under fasting conditions.
Arm 2: Nilotinib capsules 300 mg BID administered under fasting conditions.
Study burden and risks
Risk: Adverse events of the study medication.
Burden:
• Visits: Screening visit. Treatment period: During 1st 12 weeks4 times study
visit (on 1st day of treatment period and 2, 4 and 12 weeks after start of
treatment). Thereafter every 12 weeks until the end of treatment. End of
treatment visit.
• Phone call 4 weeks after end of treatment and every 12 weeks thereafter.
• Physical examination, including blood pressure, pulse, temperature, weight:
every visit.
• Blood tests (fasting for glucose and lipids, approx. 15-35 mL): every visit.
• Pregnancy test (if relevant) every month (if necessary at home, result to be
communicated to investigator by phone).
• EKG 4 times.
• Bone marrow assessment during screening, if not performed within the last 3
months. If necessary to be repeated during the treatment period.
• Questionnaires:
QLQ-C30, CML24 (every 4-24 weeks during the 1st year, end of 2nd year and end
of treatment, 3 times during follow-up).
PRO-CTCAE, FACT GP5 (every week during the 1st 6 months and every 4 weeks
thereafter, 3 times during follow-up).
Optional:
• Use of data and remaining body material for other research.
• Trial Feedback Questionnaire about the patient*s feedback on trial experience
(3 times).
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Males or females >= 18 years of age.
2. CML-CP within 3 months of diagnosis.
3. Diagnosis of CML-CP (European Leukemia Network 2020 criteria) with
cytogenetic confirmation of the Ph chromosome. Documented CML-CP will meet all
the criteria as mentioned in item 4 on page 10 of the protocol.
4. Evidence of typical BCR::ABL1 transcript. See item 5 on protocol page 10 for
details.
5. ECOG performance status of 0 or 1.
6. Adequate end organ function as defined in item 7 on protocol page 10.
7. The laboratory values mentioned in item 8 on protocol pages 10/11 must be
within normal limits or must have been corrected to within normal limits with
supplements prior to randomization
Exclusion criteria
1. Previous treatment of CML with any other anticancer agents or prior stem
cell transplant, with the exception of hydroxyurea and/or anagrelide.
2. Known cytopathologically confirmed CNS infiltration.
3. Impaired cardiac function or cardiac repolarization abnormality. See item 3
on protocol page 11 for details.
4. Severe and/or uncontrolled concurrent medical disease that in the opinion of
the investigator could cause unacceptable safety risks or compromise compliance
with the protocol. See item 5 on protocol page 11 for examples.
5. History of significant bleeding disorder. See item 5 on protocol page 11 for
details.
6. Major surgery within 4 weeks prior to study entry or not recovered from
prior surgery.
7. History of other active malignancy within 3 years prior to study entry. See
item 7 on protocol page 11 for exceptions.
8. History of acute pancreatitis within 1 year prior to randomization or
medical history of chronic pancreatitis.
9. History of chronic liver disease leading to severe hepatic impairment, or
ongoing acute liver disease.
10. Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV)
infection. See item 10 on protocol page 12 for details.
11. History of HIV unless well-controlled on a stable dose of anti-retroviral
therapy at the time of screening.
12. Impairment of GI function or GI disease that may significantly alter the
absorption of study treatment. See item 12 on protocol page 12 for details...
13. Participation in a prior investigational study within 30 days prior to
randomization or within 5 half-lives of the investigational product, whichever
is longer.
14. Pregnant or lactating women
15. Women of child-bearing potential not using highly effective methods of
contraception. See item 15 on protocol page 12 for details.
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 |
|---|---|
| EU-CTR | CTIS2024-510947-71-00 |
| EudraCT | EUCTR2022-000995-21-NL |
| ClinicalTrials.gov | NCT05456191 |
| CCMO | NL82770.056.22 |