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RecruitingPhase 1 / Phase 2

Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies

Phase Ib/II Investigator Initiated Study of the IDH1-Mutant Inhibitor Ivosidenib (AG120) With the BCL2 Inhibitor Venetoclax +/- Azacitidine in IDH1-Mutated Hematologic Malignancies

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: 3 years

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
  • "After completion of study treatment, patients are followed up at 30 days, and then monthly for 3 years."
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 venetoclax with ivosidenib, with or without azacitidine, for blood cancers with an IDH1 gene change. It looks at side effects, the best dose of venetoclax, and how well treatment works. It is for adults with certain blood cancers that have not responded to treatment, have returned, or cannot be treated with standard starting chemotherapy.

This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutated hematologic malignancies. Venetoclax and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ivosidenib and venetoclax with azacitidine may work better in treating patients with hematologic malignancies compared to ivosidenib and venetoclax alone.

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 older than 18 and able to do daily activities with little or no limitation.
  • Your cancer must have an IDH1-R132 gene change. Some other IDH1 changes may qualify with the study leader’s approval.
  • You must have acute myeloid leukemia (AML) that returned or did not respond to treatment, or untreated AML that cannot be treated with standard starting chemotherapy.
  • Certain high-risk blood or bone marrow diseases called MDS, MDS/MPN, or MPN may also qualify if standard treatment failed, with the study leader’s approval.
  • Your liver and kidneys must work well enough based on blood tests. Liver test problems caused by leukemia may be allowed.
  • You must be willing and able to give informed consent, meaning you understand and agree to join.
  • Usually, at least 7 days must pass after your last cancer treatment before study treatment starts. This may not apply if your disease is growing quickly.
  • Men must avoid unprotected sex and sperm donation from the first study dose until 90 days after the last dose.

Who can't join

  • You cannot join if you are allergic to ivosidenib or venetoclax, or have taken either drug before.
  • You cannot have an uncontrolled health problem that makes treatment unsafe, or a severe stomach, bowel, or body-chemistry problem that keeps you from absorbing the study pills.
  • Other cancer drugs are generally not allowed. Exceptions include chemotherapy into spinal fluid to prevent or control leukemia there, and limited hydroxyurea or cytarabine for fast-growing disease.
  • You cannot take certain drugs that change how the body handles medicines within 3 days before study treatment. These include avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, and St. John’s wort.
  • Active graft-versus-host disease, when donor cells attack your body after a stem cell transplant, may exclude you. Some people receiving ongoing treatment may qualify with the study leader’s approval.
  • You cannot have another active cancer being treated, active hepatitis B or C, or a known HIV infection.
  • You cannot have a heart rhythm test result called QTcF over 450 milliseconds unless the study leader approves. Your white blood cell count must be 25 billion per liter or less; hydroxyurea may be used to lower it.
  • You cannot be breastfeeding or have a positive pregnancy test. If you can become pregnant, you must agree to use effective birth control.

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

Official eligibility criteria

Inclusion Criteria: 1. Age \> 18 years. 2. ECOG performance status of \< 2. 3. IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the PI. 4. Relapsed/refractory AML, or treatment-naïve patients with AML who are not eligible for standard induction chemotherapy. Patients with high-risk MDS, MDS/MPN or MPN (defined as \> 10% bone marrow blasts, or intermediate or high risk by IPSS, R-IPSS or D-IPSS) that have failed standard therapy may also be eligible after discussion with the PI. 5. Adequate hepatic function (direct bilirubin \< 2 x ULN, ALT and/or AST \< 3x ULN) unless deemed to be related to underlying leukemia. 6. Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation. 7. Willing and able to provide informed consent 8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. 9. Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug. Exclusion Criteria: 1. Patients with known allergy or hypersensitivity to ivosidenib or venetoclax. 2. Patients who have previously received either ivosidenib or venetoclax. 3. Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment. 4. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea and/or one dose of cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. 5. Patients receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's wort) within 3 days of start of study therapy. 6. Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI). 7. Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications. 8. Patients with a concurrent active malignancy under treatment. 9. QTc interval using Fridericia's formula (QTcF) \> 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI. 10. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection. 11. Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea is permitted to meet this criterion.) 12. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception a. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).

Study sites (4)

MA

OH

OR

TX