RecruitingPhase 2

A Study of the Combination of Ivosidenib, Azacitidine, and Venetoclax Followed by Ivosidenib Alone in People With Acute Myeloid Leukemia

A Phase II Study of IDH1 Inhibition With Ivosidenib as Maintenance Therapy After Ivosidenib, Azacitidine, and Venetoclax for Acute Myeloid Leukemia

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
60 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests three drugs—ivosidenib, azacitidine, and venetoclax—followed by ivosidenib alone to help keep cancer from coming back. It is for people age 60 or older with newly diagnosed acute myeloid leukemia (AML), a blood cancer, with a certain IDH1 gene change. Researchers will check how well treatment works, its safety, and how much time it takes.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You are at least 60 years old when you sign the consent form.
  • You can and will follow the study visit schedule and other study rules.
  • You have newly diagnosed AML.
  • Lab testing shows an IDH1-R132 gene change before treatment starts. Some other IDH1 changes may qualify after review by the study leader.
  • Your ability to do daily activities meets the study's rating of 0–3. This can include needing help with some self-care.
  • Your white blood cell count is below 25,000 per microliter when treatment starts. Treatment to lower this count is allowed.
  • Your liver and kidney blood tests meet the study's limits. Some liver test exceptions are allowed.

Who can't join

  • You have acute promyelocytic leukemia, a certain type of AML.
  • You have taken ivosidenib or venetoclax before, or are taking another experimental cancer drug. Hydroxyurea to lower blood cell counts is allowed.
  • You have severe, life-threatening leukemia problems, such as uncontrolled bleeding, pneumonia with low oxygen or shock, or widespread blood clotting.
  • You have an active infection that is not improving with proper treatment. This includes HIV, hepatitis B, or hepatitis C if it is not improving with treatment.
  • Your doctor plans for you to have a stem cell transplant using cells from a donor.
  • You have had serious active heart disease or a stroke within the past 6 months, or have certain heart rhythm test results or risks.
  • You have trouble swallowing or a condition that limits how well your body takes in medicines by mouth.
  • You are not willing to follow the study's birth control rules.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 exclusion criteria 5, patients receiving appropriate treatment would only be excluded if there is no improvement. * Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. * Participant has QTc interval (i.e., Fridericia's correction \[QTcF\]) ≥ 450 ms (mean of triplicate ECG) or other factors that increase the risk of QT prolongation or ventricular arrhythmic events (e.g. family history of long QT interval syndrome). Participants with a QTcF over 450 ms due * Male or female participants not willing to comply with contraceptive requirements

Study sites (7)

NJ

NY