Leukemia, Chronic Myeloid
Conditions
Keywords
Asciminib, CML-CP, Philadelphia chromosome-positive, Real-world evidence, Non-interventional study, Germany, BCR::ABL1, Major Molecular Response, Adherence, MARS-5, EORTC QLQ-C30, EORTC QLQ-CML24, WPAI-GH, Tyrosine kinase inhibitors
Brief summary
The aim of this study is to assess the real-world effectiveness of asciminib in Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) patients who were either newly diagnosed or previously treated with one ATP-competitive tyrosine kinase inhibitor (TKI).
Interventions
None listed
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before participation in the study/prior to any study-related documentation. 2. Adult patients (≥18 years of age) with a confirmed diagnosis of Ph+ CML-CP. The presence of the Philadelphia chromosome may alternatively be confirmed by molecular detection of a BCR::ABL1 fusion gene/transcript (e.g., by reverse transcription polymerase chain reaction (RT-PCR)), in accordance with the World Health Organization (WHO) 2022 classification. 3. Patients who are either newly diagnosed or have received treatment with exactly one prior TKI. Prior TKI treatment is only permitted for patients in the Asciminib Cohort. Patients in the comparator cohorts (imatinib, dasatinib, bosutinib, nilotinib) must be newly diagnosed and must not have received any prior TKI treatment. 4. Patients for whom the treating physician has made a clinical decision to initiate treatment with asciminib or another TKI (imatinib, dasatinib, bosutinib, nilotinib) as part of routine care. The clinical decision for treatment must have been made prior to enrollment. Treatment must not have started more than 14 days before study inclusion, and treatment may also begin after baseline assessment. 5. Patients willing to participate in routine follow-up visits and complete patient-reported outcome questionnaires over the course of the study.
Exclusion criteria
1. Patients with contraindications to their respective chronic myeloid leukemia (CML) treatment as per the applicable Summary of Product Characteristics (SmPC) and relevant national treatment guidelines (e.g. Onkopedia CML), as well as additional disease- or treatment-related characteristics associated with distinct clinical scenarios that differ from the intended study population, including situations with specific treatment requirements or limited comparability, in which reliable interpretation of study outcomes may not be feasible, including the following asciminib specific considerations: * In first- or second-line treatment: presence of BCR::ABL1 fusion transcripts lacking exon a2 (e.g. e13a3, e14a3, e1a3). * In second-line treatment: * known BCR::ABL1 mutations associated with partial or complete resistance to asciminib (e.g. M244V, F359I/V/C). * presence of the BCR::ABL1 T315I mutation, regardless of eligibility for treatment according to SmPC (e.g., specific indication and dosing regimens). 2. Patients receiving or planned to receive asciminib or other TKIs outside the approved label (off-label use), including use in unapproved dosing regimens or frequency not covered by the respective SmPC. 3. Patients currently participating in an interventional clinical trial. 4. Patients unable or unwilling to provide written informed consent. 5. Patients who are unable to reliably complete patient-reported outcome questionnaires due to cognitive or language limitations relevant to the study assessments. 6. Patients for whom long-term follow-up is not feasible due to expected relocation or other logistical constraints. 7. The restriction to a maximum of one prior ATP-competitive TKI applies exclusively to patients treated with asciminib. Patients in the comparator cohorts (imatinib, dasatinib, bosutinib, nilotinib) must be TKI-naïve and are included at the start of their first-line TKI therapy and are not eligible if they have received any prior TKI treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Major Molecular Response (MMR) at 12 Months | Month 12 | MMR is defined as a BCR::ABL1 level ≤ 0.1% according to the International Scale (IS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients by Clinical Characteristic | Baseline | Characteristics include, but are not limited to, detection of Philadelphia chromosome or BCR::ABL1 transcript, prior treatment, and Eastern Cooperative Oncology Group (ECOG) performance status. |
| Percentage of Patients by Reason for TKI Treatment Decision Documented by the Treating Physician | Baseline | — |
| Percentage of Patients With Dose Reduction by Reason for Dose Reduction | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Percentage of Patients With Treatment Interruption by Reason for Interruption | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Percentage of Patients Who Discontinued Treatment by Reason for Discontinuation | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Time to Treatment Discontinuation | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Time to Treatment Interruption | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Time to Dose Reduction | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Time to Treatment Discontinuation due to Adverse Events (TTDAE) | 3, 6, 9, 12, 15, 18, 21, and 24 months | — |
| Percentage of Patients With Early Molecular Response (EMR) at 3 Months | Month 3 | EMR is defined as BCR::ABL1 ≤10% IS. |
| Percentage of Patients With Molecular Response 2 (MR2) | 3, 6, 9, 12, 15, 18, 21, and 24 months | MR2 is defined as BCR::ABL1 ≤1% IS. |
| Percentage of Patients With MMR | 3, 6, 9, 15, 18, 21, and 24 months | MMR is defined as BCR::ABL1 ≤0.1% IS. |
| Percentage of Patients With Deep Molecular Response: MR4.0 | 3, 6, 9, 12, 15, 18, 21, and 24 months | Deep Molecular Response (MR4.0): ≤0.01% BCR::ABL1 IS and Reference gene copies \>10,000 ABL1 or \>24,000 GUSB. |
| Percentage of Patients With Deep Molecular Response: MR4.5 | 3, 6, 9, 12, 15, 18, 21, and 24 months | Deep Molecular Response (MR4.5): ≤0.0032% BCR::ABL1 IS and Reference gene copies \>32,000 ABL1 or \>77,000 GUSB. |
| Percentage of Patients With Deep Molecular Response: MR5 | 3, 6, 9, 12, 15, 18, 21, and 24 months | Deep Molecular Response (MR5): ≤0.001% BCR::ABL1 IS and Reference gene copies \>100,000 ABL1 or \>240,000 GUSB. |
| Medication Adherence Report Scale (MARS-5) Score | 3, 6, 9, 12, 15, 18, 21, and 24 months | The MARS-5 questionnaire is a validated self-report questionnaire developed to assess patient adherence to prescribed medication, focusing on both intentional and unintentional non-adherence. It consists of 5 items, each rated on a 5-point Likert Scale from 0 (always) to 5 (never). The total score ranges from 5 to 25, with higher scores indicating better adherence to treatment. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score | 3, 6, 9, 12, 15, 18, 21, and 24 months | The EORTC QLQ-C30 contains 30 questions answered by the patient. There are 9 multiple-item scales: 5 scales that assess aspects of functioning (physical, role functioning, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health status/Quality of Life (QOL) scale. There are 5 single-item measures assessing additional symptoms (i.e., dyspnea, loss of appetite, insomnia, constipation, and diarrhea) and a single item concerning perceived financial impact of the disease. All but 2 questions have 4-point scales ranging from "Not at all" to "Very much." The 2 questions concerning global health status/QOL have 7-point scales with ratings ranging from "Very poor" to "Excellent." For each of the 14 domains, final scores are transformed such that they range from 0-100, where higher scores indicate improvement. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for CML (EORTC QLQ-CML24) Score | 3, 6, 9, 12, 15, 18, 21, and 24 months | The EORTC QLQ-CML24 was designed to supplement the QLQ-C30 - the QLQ-CML24 is not a stand-alone instrument but is to be used in conjunction with the QLQ-C30. The EORTC QLQ-CML24 is composed of 4 multi-item scales and 2 single-item scales. The module consists of 24 items assessing symptom burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items are measured on 4 levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores are averaged and transformed to 0 to 100. A higher score in symptom burden, impact on worry/mood, impact on daily life, and body image problems domains indicates a worse outcome. A higher score in satisfaction with social life and satisfaction with care and information domains indicates a higher level of satisfaction. |
| Work Productivity and Activity Impairment - General Health (WPAI-GH) Score | 3, 6, 9, 12, 15, 18, 21, and 24 months | The WPAI-GH is a patient-reported 6 item questionnaire which addresses absenteeism, presenteeism, overall work productivity loss, and activity impairment for the 7 days prior to the assessment. Work productivity and activity impairment outcomes are presented as impairment percentages ranging from 0 to 100 with a higher percentage indicating greater impairment and less productivity. |
Countries
Germany
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed