Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

Inclusion Criteria

• •1. Morphological diagnosis of AML (WHO criteria 2022)
• •2. Newly diagnosed AML.
• •3. IDH1 R132 mutations (centrally assessed by PCR and NGS). A patient will be allowed to be included with local result after approval of the medical monitor.
• •4. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2 if ≥ 60 years of age, or 0 to 3 if ≥ 18 to 60 years.
• •5. Age ≥ 18 years with comorbidities contraindicating intensive chemotherapy; or age ≥ 60 years.
• •* ≥ 60 years of age;
• •* or ≥ 18 to 60 with at least one of the following co-morbidities:
• •* ECOG Performance Status of 2 or 3;
• •* Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 55% or chronic stable angina;
• •* DLCO ≤ 65% or FEV1 ≤ 65% or significant history of chronic pulmonary obstructive;
• •* Creatinine clearance ≥ 25 mL/min to \< 50 ml/min
• •* Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × ULN
• •* Non active/controlled prior neoplastic disease
• •* Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the PETHEMA medical monitor before study enrolment (e.g, prior MDS or MPS, high-risk cytogenetics)
• •6. Patients \<70 years, with favorable risk AML according to ELN will be included only if they are not candidates to standard treatment with intensive chemotherapy.
• •7. Adequate renal function as demonstrated by a creatinine clearance ≥ 25 mL/min (calculated by the Cockcroft Gault formula).
• •8. Adequate liver function as demonstrated by: aspartate aminotransferase (AST) ≤ 5.0 × ULN, alanine aminotransferase (ALT) ≤ 5.0 × ULN, bilirubin ≤ 2.5 × ULN (unless considered to be due to leukemic disease, in which case it should be approved by the PETHEMA medical monitor).
• •9. Subject has a white blood cell count \< 30 × 109/L (Hydroxyurea is permitted to meet this criterion)
• •10. Female subjects must be either postmenopausal OR permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) OR Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control. Female subjects of childbearing potential must have negative results for pregnancy tests performed along the study (screening and every three cycles). A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
• •11. Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception.
• •12. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.