RecruitingPhase 2

Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax

Pilot Single Arm Phase 2 Study of Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax

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

  • Time periods mentioned: 28 days

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Each cycle will last for 28 days."
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 olutasidenib for adults with acute myeloid leukemia (AML), a blood cancer, with a change in the IDH1 gene. It is for people whose AML came back or did not respond to treatment and got worse after treatment with venetoclax. Another drug, azacitidine, may be added after 3 treatment cycles if signs of leukemia have not fully cleared.

This is a prospective, single-arm phase 2 pilot study to assess the response rate of IDH1 mutated relapsed/refractory acute myeloid leukemia (AML) patients who receive olutasidenib after progressing on venetoclax based regimens. Each cycle will last for 28 days. Patients will receive olutasidenib 150 mg orally twice daily Day 1 through Day 28. After 3 cycles of olutasidenib, azacitidine 75 mg/m2 given on Day 1 through Day 7 may be added at the discretion of the treating investigator if the patient has not achieved a complete remission. Subjects with at least a PR after 6 cycles of treatment will continue treatment as previously described. Subjects without at least a partial response (PR) after 6 cycles of treatment will move to long term follow up.

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

Eligibility

Who can join

  • Be age 18 or older, sign a consent form, allow use of health information, and be able to follow study steps.
  • Have AML confirmed by testing that came back or did not respond to treatment, with an IDH1 gene change.
  • Have had no more than 2 prior courses of treatment for AML, including one with venetoclax.
  • Be able to care for yourself and be up and about for more than half of waking hours.
  • Have no more than moderate lasting side effects from past treatment, except blood-related problems or infections. Kidney and liver blood tests must meet study limits.
  • If able to become pregnant, have a negative blood pregnancy test. If sex could lead to pregnancy, use effective birth control or avoid vaginal sex.
  • If you have HIV, be on effective treatment with no virus detected in the blood within the past 6 months.
  • If you have hepatitis B, have no virus detected in the blood, with treatment if needed. Hepatitis C must be cured, or you must be on treatment with no virus detected.

Who can't join

  • Have taken ivosidenib or another drug that blocks IDH1.
  • Have an active infection needing medicine through a vein. Antibiotics taken to prevent infections are allowed.
  • Have AML in the brain or spinal cord.
  • Have had a stem cell transplant from a donor within 60 days before joining.
  • Have recently used an experimental drug. The study sets a waiting period based on 21 days or how long the drug stays in the body.
  • Have had a severe allergic reaction to olutasidenib or its ingredients, or are pregnant or breastfeeding.
  • Have another cancer whose course or treatment could affect study safety or results.
  • Take certain medicines or supplements that affect how the body processes drugs. These require a waiting period of at least 2 weeks, sometimes longer, before starting olutasidenib.

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

Official eligibility criteria

Inclusion Criteria: 1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of ≤ 2 within 28 days prior to registration. 4. Must have histologically or cytologically documented relapsed and/or refractory Acute Myeloid Leukemia (Refractory is defined as failure to achieve a CR after induction chemotherapy or a minimum of two cycles of HMA plus venetoclax) 5. Acute Myeloid Leukemia with a documented IDH1 mutation. 6. No more than 2 lines of prior therapy. NOTE: One line of therapy must have contained venetoclax. 7. Persisting, non-hematologic and non-infectious toxicities from prior treatment must be Grade ≤ 2. NOTE: Documentation of these criteria is required at screening. 8. Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration. * Renal * Calculated creatinine clearance (Cockcroft-Gault formula will be used to calculate creatinine clearance) ≥ 30 mL/min * Hepatic * Total bilirubin2 ≤ 2× upper limit of normal (ULN); ≤ 3 times ULN in patients with Gilbert Syndrome * Aspartate aminotransferase (AST) ≤ 5 × ULN * Alanine aminotransferase (ALT) ≤ 5× ULN 9. Participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. 10. Participants of childbearing potential who are having penile-vaginal intercourse with a person able to father a child must be willing to abstain from penile-vaginal intercourse or must use an effective method(s) of contraception. A participant able to father a child who is having penile-vaginal intercourse with a person of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. 11. Subjects with known HIV infection may be eligible if they are on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration. Testing is not required at screening. 12. Subjects with known chronic hepatitis B virus (HBV) infection may be eligible if they have an undetectable HBV viral load on suppressive therapy, if indicated. Subjects with a history of hepatitis C virus (HCV) infection may be eligible if they have been treated and cured. Subjects with an HCV infection who are currently on treatment must have an undetectable HCV viral load to be eligible for this trial. Testing is not required at screening. 13. As determined by the investigator or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria: 1. Previous exposure to ivosidenib or any IDH1 inhibitor. 2. Active infection requiring IV systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. 3. Known CNS involvement with AML. 4. Previous allogeneic stem cell transplant within 60 days prior to registration. 5. Treatment with any investigational drug within 21 days or 2 half-life's prior to registration. 6. History of severe allergic anaphylactic reactions to olutasidenib or any of their excipients. 7. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the subject is being treated on study. 8. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion. 9. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olutasidenib is 2 weeks or 5 half-lives (whichever is longer) prior to initiation of treatment. 10. Concomitant use of known sensitive CYP3A substrates (e.g. Midazolam, simvastatin, fluticasone, budesonide). The required washout period prior to starting olutasidenib is 2 weeks or 5 half-lives (whichever is longer) prior to initiation of treatment.

Study sites (1)

NC