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A Phase 3b study to learn more about the safety and tolerability of ivosidenib in combination with azacitidine in adult patients newly diagnosed with IDH1m acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy

Phase 1
Recruiting
Conditions
Isocitrate deshydrogenase1 mutation-positive (IDH1m) acute myeloid leukemia (AML)
MedDRA version: 21.0Level: LLTClassification code: 10000886Term: Acute myeloid leukemia Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]
Registration Number
CTIS2022-501709-11-00
Lead Sponsor
Servier Affaires Medicales
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
233
Inclusion Criteria

Has previously untreated AML, defined according to the 2022 ELN Recommendations for AML or the International Consensus Classification of myeloid neoplasms and acute leukemia, Be =18 years of age and meet at least one of the following criteria defining ineligibility for IC: a. =75 years old b. ECOG PS =2 c. Any comorbidity that the Investigator judges to be incompatible with IC, including: i. Severe cardiac disorder ii. Severe pulmonary disorder iii. Creatinine clearance <45 mL/minute iv. Bilirubin >1.5 times upper limit of normal (× ULN) v. Any other comorbidity that the Investigator judges to be incompatible with IC as documented before study enrolment., Has documented R132 IDH1m based on local biomolecular profiling method, Has an ECOG =2., Has adequate hepatic function as evidenced by Child-Pugh class A or B, Has adequate renal function, as described in the protocol, Willing to voluntarily provide written, signed, and dated informed consent.

Exclusion Criteria

Has received any prior treatment for AML with the exception of hydroxyurea or leukapheresis for white count control, Has a prior history of malignancy other than MDS or myeloproliferative disorder under active treatment. However, a patient with the following history/concurrent conditions or similar indolent cancer are allowed to participate in the study: a. Basal or squamous cell carcinoma of the skin b. Carcinoma in situ of the cervix c. Carcinoma in situ of the breast d. Incidental histologic finding of prostate cancer, Has had significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke, Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs, Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, organ failure and/or disseminated intravascular coagulation, Has extramedullary disease alone (i.e., no detectable bone marrow and no detectable peripheral blood AML), Has previously received treatment for an antecedent hematologic disorder, including investigational agents, may not be enrolled until a washout period of =5 half-lives of the investigational or standard of care agent have elapsed since the last dose of that agent (Note: previous treatment with HMA for MDS is allowed), Has received prior treatment with an IDH1 inhibitor, Has a known hypersensitivity to any of the components of ivosidenib or azacitidine, Is a woman who is pregnant or breastfeeding, Is taking known strong cytochrome P450 (CYP) 3A4 inducers, inhibitors or sensitive CYP3A4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications or unless the patient can be properly monitored during the study, Is taking P-glycoprotein (P-gp) transporter-sensitive substrate medications or inhibitors unless they can be transferred to other medications or unless the patient can be properly monitored during the study, Has an active, uncontrolled, systemic fungal, bacterial, or viral infection (including human immunodeficiency virus [HIV], active hepatitis B (HBV), or hepatitis C virus [HCV]) without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
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