Acute Myeloid Leukemia
Conditions
Keywords
Ivosidenib, Azacitidine, Venetoclax, 25-224
Brief summary
The researchers are doing this study to find out whether a 3-drug combination of ivosidenib, azacitidine, and venetoclax followed by maintenance therapy with ivosidenib alone is an effective treatment approach for people with newly diagnosed acute myeloid leukemia (AML) that has an IDH mutation. Maintenance therapy is additional treatment given to help keep cancer from coming back after it has disappeared following the first course of treatment. The researchers will also look at the safety of the treatment approach and what kind of a time commitment it involves for participants.
Interventions
DRUGIvosidenib
Ivosidenib ( days 15 through 28 for cycle 1, then days 1 through 28 for each cycle thereafter)
DRUGAzacitidine
Azacitidine (IV or SC per institutional preference, days 1 through 7)
DRUGVenetoclax
Venetoclax (days 1 through 14)
Sponsors
Memorial Sloan Kettering Cancer Center
Servier Pharmaceuticals, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase II, single-arm, multicenter clinical trial.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be at least 60 years of age at the time of signing the informed consent form (ICF). * Participant is willing and able to adhere to the study visit schedule and other protocol requirements. * Participant has newly diagnosed AML as per World Health Organization 2022 or European leukemia Network 2022 guidelines. * Participant has IDH1-R132 mutation present prior to initiating Ivo/Aza/Ven confirmed by CLIA approved local testing via next-generation sequencing (NGS) and/or polymerase chain reaction (PCR). Other 2-HG producing IDH1 variants may be eligible after discussion with MSK principal investigator. 1. At MSK, this testing will utilize the MSK-REACT, a rapid multi-gene NGS panel used in all new AML diagnoses that is clinically validated by the Laboratory of Diagnostic Molecular Pathology pursuant to the requirements of CLIA'88 and approved by New York State. Other sites may use local CLIA-certified laboratories and validated clinical assays as per standard of care. 2. The patient's chart will be utilized for screening purposes * Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 * Participant must have a WBC count \<25,000/μL at the time of initiation of study drug (leukapheresis may be performed and/or hydroxyurea may be administered to decrease the WBC count to \<25,000/μL). * Participant has adequate organ function defined as: 1. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement. 2. Serum total bilirubin \< 3.0 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, leukemia organ involvement or Gilbert's syndrome. 3. Serum creatinine \< 2 x ULN or creatinine clearance 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.
Exclusion criteria
* Participant with acute promyelocytic leukemia * Participants who have previously received ivosidenib or venetoclax * Participant receiving any other investigational anti-cancer agents. Cytoreductive therapy such as hydroxyurea is permitted. * Participants with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation * Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment). * Participants who are planned for allogeneic stem cell transplantation based on the assessment of the treating clinician. * Participant has significant active cardiac disease within 6 months prior to start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke * Participant has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). As per
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival | 12 months | Event-free survival is defined as the time between date of treatment start to treatment failure (failure to achieve complete remission or \<5% bone marrow blasts), confirmed relapse or death. |
Countries
United States
Contacts
CONTACTKuo-Kai Chin, MD
CONTACTEytan Stein, MD
PRINCIPAL_INVESTIGATORKuo-Kai Chin, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed