Clinical trial NCT06945146: Genomics Study in CML Patients With Ponatinib Treatment
Official title: The Comprehensive Assessment of BCR-ABL1 Gene Expression and Genetic Variations by qRT-PCR and NGS Assays in Chronic Myeloid Leukemia Patients Who Are Treated With Ponatinib (CAP Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Keywords: ponatinib
tyrosine kinase inhibitor
resistance
intolerance
genetic variation
next generation sequencing
Lead sponsor: Eulji University Hospital
Sponsor class: OTHER
Collaborators: name: Ulsan National Institute of Science and Technology
name: Takeda
First posted: 2025-04-25
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will involve 100 patients with BCR-ABL1-positive CML who failed to prior targeted therapy other than ponatinib. Patients receiving ponatinib 45 mg once daily as a second-line or later therapy will be enrolled.

Brief summary: This study will evaluate whether responsiveness and adverse events (AEs) to second-line or later ponatinib treatment are associated with genetic variations as measured by real-time quantitative polymerase chain reaction (qRT-PCR) and next-generation sequencing (NGS) in patients with CML of any stage who failed prior multiple targeted therapies except ponatinib.

Detailed description: Ponatinib treatment will be initiated per usual treatment procedure at 45 mg once daily p.o., which will be gradually decreased to 30 mg and 15 mg according to the predefined criteria based on responsiveness to treatment and AEs in the course of the treatment. A total of 100 subjects will be enrolled within 24 months after the first subject enrollment, and ponatinib treatment will continue for 24 months after the initial dosing of ponatinib in each enrolled subject. Routine ponatinib treatment will continue at the investigator's discretion until disease progression, the occurrence of unacceptable toxicity, subject's withdrawal of consent, or occurrence of any reason for discontinuation specified in the protocol.

All molecular analysis samples will be collected, transferred, and managed by the Catholic Leukemia Research Institute, and NGS will be performed.

\<Eligibility\>

1. Adults with BCR-ABL1-positive CML
2. Subjects who were resistant or intolerant to prior targeted therapy other than ponatinib and with an indication for ponatinib treatment according to the acceptance criteria by the Ministry of Food and Drug Safety (MFDS)
3. Women of childbearing potential (WOCBP) should have a negative serum or urine pregnancy test (with a sensitivity of at least 25 IU/L or equivalent to HCG) within 24 hours before initiating ponatinib treatment
4. Written informed consent to ponatinib treatment

\<Outcome Measures\>

1. Primary endpoint

   - 24 months dynamics of BCR-ABL1 gene expression by qRT-PCR
2. Secondary endpoints

   * Type and frequency of novel genetic variations (mutations, gene expressions, CNV, INDEL, etc.)
   * Cobll1/GCA/novel gene network identification: functional tests using Western blot/Knock-down assay
3. Safety endpoints : To explore the dynamics of adverse events according to dose changes up to 24 months

   * Frequency and severity of skin rash, fever, hypertension, pancreatitis and vascular events as common adverse events
   * Frequency and severity of rare adverse events
   * Treatment intolerance is defined as recurrence of a Grade ≥3 hematologic AE, or a Grade ≥2 non-hematologic AE requiring permanent discontinuation of ponatinib per protocol despite dose reduction

Eligibility criteria: Inclusion Criteria:

* Patients who are willing to and capable of providing informed consent
* Adults with BCR-ABL1-positive CML

  1. Males and females aged 18 years and above
  2. Adequate organ function
* Subjects who were resistant or intolerant to prior targeted therapy other than ponatinib and with an indication for ponatinib treatment according to the acceptance criteria by the Ministry of Food and Drug Safety (MFDS)
* Women of childbearing potential (WOCBP) should have a negative serum or urine pregnancy test (with a sensitivity of at least 25 IU/L or equivalent to HCG) within 24 hours before initiating ponatinib treatment
* Female subjects who are not breastfeeding

Exclusion Criteria:

* Patients who were previously treated with ponatinib
* Patients aged below 18 years of age
* Diagnosis of severe comorbidity at baseline
* Any other cancers within 3 years

Primary outcomes:
measure: Dynamics of BCR-ABL1 gene expression by qRT-PCR
timeFrame: 24 months
Secondary outcomes:
measure: Type and frequency of novel genetic variations (mutations, gene expressions, CNV, INDEL, etc.)
timeFrame: 24 months
measure: Cobll1/GCA/novel gene network identification: functional tests using Western blot/Knock-down assay
timeFrame: 24 months
Other outcomes:
measure: Frequency and severity of skin rash, fever, hypertension, pancreatitis and vascular events as common adverse events and Frequency and severity of rare adverse events
timeFrame: 24 months
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
Study officials:
affiliation: Eulji University
name: Dong-Wook Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: