RecruitingPhase 1

Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

Who can join

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

Age
18 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 AG-120, a drug taken by mouth, in adults with advanced blood cancers that have an IDH1 gene change. It aims to find a safe dose, learn how the drug acts in the body, and see how well it works. A smaller part studies myelodysplastic syndrome, a bone marrow disease, that has come back or has not responded to treatment.

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced hematologic malignancies that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where four cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Additionally, the study includes a substudy evaluating the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome with an IDH1 mutation. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

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

Eligibility

Who can join

  • You must be 18 or older and have an advanced blood cancer with a confirmed IDH1 R132 gene change.
  • You must agree to repeated bone marrow tests and blood and urine samples.
  • You must be able to care for yourself and be up and about for at least half of your waking hours.
  • Your platelet count must be at least 20,000/µL. Platelets help blood clot. Blood transfusions to reach this level are allowed.
  • Your liver blood tests must meet study limits. Some exceptions apply if the results are due to leukemia or Gilbert’s disease.
  • Your kidneys must work well enough based on the study’s blood test or kidney filtering limits.
  • You must have recovered from important side effects of past surgery, radiation, or other cancer treatment.
  • If you can become pregnant, you must have a negative blood pregnancy test within 7 days before treatment and on the first treatment day.

Who can't join

  • You had a blood-forming stem cell transplant within 60 days, take drugs to weaken the immune system after a transplant, or have serious graft-versus-host disease, where donor cells attack your body. Some steroid use is allowed.
  • You had cancer drug treatment, radiation, or an experimental drug less than 14 days before starting the study drug. Hydroxyurea is allowed.
  • You are pregnant or breastfeeding.
  • You have a severe active infection or an unexplained fever above 38.5°C at screening or on the first treatment day. The study doctor may allow fever caused by the cancer.
  • You have serious heart failure, heart pumping strength below 40%, a heart attack within the past 6 months, uncontrolled chest pain, or a history of severe or uncontrolled abnormal heart rhythms.
  • Your heart rhythm test shows a QTc of 450 milliseconds or more, you have other risks for dangerous heart rhythms, or you take drugs that lengthen the QT interval, part of the heart’s electrical cycle.
  • You have known HIV, active hepatitis B or C, or known or suspected leukemia in the brain or spinal cord.
  • You have life-threatening problems from leukemia, such as uncontrolled bleeding, pneumonia with low oxygen or shock, or severe blood-clotting problems.

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

Official eligibility criteria

Key Inclusion Criteria: * Subject must be ≥18 years of age. * Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation. * Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study. * Subjects must have ECOG PS of 0 to 2. * Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed). * Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic disease * Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or creatinine clearance \>40mL/min based on Cockroft-Gault glomerular filtration rate (GFR) * Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. * Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration. Key Exclusion Criteria: * Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin GVHD is permitted.) * Subjects who received systemic anticancer therapy or radiotherapy \<14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120). * Subjects who received an investigational agent \<14 days prior to their first day of study drug administration. * Subjects who are pregnant or breastfeeding. * Subjects with an active severe infection or with an unexplained fever \>38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled). * Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1. * Subjects with a history of myocardial infarction within the last 6 months of screening. * Subjects with a known unstable or uncontrolled angina pectoris. * Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias. * Subjects with known unstable or uncontrolled angina pectoris. * Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events. * Patients taking medications that are known to prolong the QT interval * Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C. * Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. * Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

Study sites (26)

AL

AZ

CA

CO

FL

GA

IL

MA

MD

MI

MO

NC

NY

OH

OR

SC

TN

TX