Ivosidenib (TIBSOVO®) Combined With Azacitidine According to Current SmPC

Study Overview
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Brief Summary
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The goal of this non-interventional study is to evaluate quality of life (QoL) in adult patients with newly diagnosed IDH1 R132-mutated AML who are not eligible to receive standard induction chemotherapy and who are treated with ivosidenib in combination with azacitidine in a real-world setting in Germany. The main questions it aims to answer are: Evaluate QoL by validated and widely used Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) questionnaire and European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) questionnaire during treatment and follow-up period Assesment of effectiveness in routine treatment (e.g. overall survival, event-free survival, overall response rate) Assessment of drug safety (all adverse events) Description of treatment reality in detail

Official Title
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Ivosidenib in Combination With Azacitidine as First-line Treatment for Adult Patients With Newly Diagnosed AML With an IDH1 R132 Mutation Who Are Not Eligible to Receive Standard Induction Chemotherapy

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Drug: Ivosidenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Newly diagnosed Acute Myeloid Leukemia (AML). Having an isocitrate dehydrogenase 1 (IDH1) R132 mutation. Not eligible to receive standard induction chemotherapy. Decision for treatment with ivosidenib in combination with azacitidine as per current SmPC. Signed written informed consent before start of study treatment. For patients participating in PROs: Willingness and capability to participate in PRO assessment in German language Other criteria according to current SmPC. Exclusion Criteria: Participation in an interventional clinical trial within 30 days prior to enrollment or simultaneous participation in an interventional clinical trial except for the follow-up period. Patients unable to consent Other contraindications according to current SmPC.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ivosidenib|inhibitor of mutant IDH1|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate quality of life | Validation of FACT-Leu. Change from baseline (treatment start) of FACT-Leu total score | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective well-being: Validation of FACT-Leu | Change from baseline (treatment start) of FACT_Leu subscale score | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Subjective well-being: Validation of FACT-Leu | Time to deterioration of FACT-Leu total score | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Subjective well-being: Validation of FACT-Leu and EQ-5D-5L questionnaire | Change from baseline and TTD of FACT-G total score | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Subjective well-being: Validation of FACT-Leu and EQ-5D-5L questionnaire | Trial Outcome Index | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Subjective well-being: Validation of EQ-5D-5L questionnaire | Change from baseline of the EQ-5D-5L visual analogue scale (VAS) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Subjective well-being: Validation of EQ-5D-5L questionnaire | Index value of EQ-5D-5L over time | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assesment of effectiveness in routine treatment | Assesment of overall survival (OS), | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assesment of effectiveness in routine treatment | Event-free survival (EFS) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assesment of effectiveness in routine treatment | Overall Response Rate (ORR; i.e. CR, CR with incomplete hematologic recovery (Cri), (including CR with incomplete platelet recovery (CRp), CR with partial hematologic recovery (CRh), or partial recovery (PR)), Duration of CR (DOCR), Duration of Response (DOR; CR, Cri, CRp, CRh, PR)) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assesment of effectiveness in routine treatment | Time to first response (TTR) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assessment of drug safety | Assesment of adverse events (AEs), serious adverse events (SAEs), adverse drug reactions (ADRs), serious adverse drug reactions (SADRs), Adverse events of special interest (AESIs) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Assessment of parameters of treatment decision making | Frequency of distinct parameters affecting therapy choice including reasons why patient is ineligible for standard induction chemotherapy. | From date of patient enrollment until start of treatment | 
| Ivosidenib and azacitidine treatment: Dose intensity | Descriptive statistics will be provided for dose intensity for ivosidinib and azacitidine | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Ivosidenib and azacitidine treatment: Frequency and type of dose modification | Frequency tabels will be provided for frequency and type of dose modification for ivosidinib and azacitidine | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Ivosidenib and azacitidine treatment: Reason for dose modifications | Frequeny tabels of reasons for dose modifications will be provided for ivosidinib and azacitidine | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Ivosidenib and azacitidine treatment: Duration of treatment in total and for each substance | Descriptive statistics will be provided for duration of treatment in total and for each substancedose | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Ivosidenib and azacitidine treatment: Reason for end of treatment (EOT) | Frequency tabels of EOT-reasons will be provided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Transfusion dependency | Proportion of transfusion dependent patients to independency and vice versa will be provided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Concomitant medication | Frequency table of concomitant medication in total and frequency of concomitant medications known to induce QT prolongation (e.g., antiarrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) as well as strong CYP3A4 inducers or dabigatran will be provided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Subsequent antineoplastic therapies | Description of frequency and type of subsequent antineoplastic therapies by line of therapy (number and substance) | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Frequency of hospitalizations/emergency room visits | Frequency tabel of hospitalization and emergency room visits will be provided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Reasons for hospitalizations/emergency room visits | Frequency tabel of reasons for hospitalization and emergency room visits will be provided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 
| Treatment reality in detail: Length of hospital stay | Descriptive statistic for length of hospital stay will be privided | Baseline until end of study (during invosidinib treatment and Follow-Up); Up to 54 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IDH1 R132 mutation