Mutant IDH1 Inhibitor OlutasidenibPhase 1/2NCT06445959
Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib
A Phase 1/2 study testing Olutasidenib, Venetoclax and Decitabine in people with Mutant IDH1 Inhibitor Olutasidenib, run by M.D. Anderson Cancer Center at 5 sites in United States.
Trial summary
To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mutant IDH1 Inhibitor Olutasidenib
- What is being tested?
- Olutasidenib, Venetoclax and Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 5 sitesUnited States
- Study dates
- 29 Aug 2024to 30 Jun 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Participants must have a documented IDH1 gene mutation
- Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR
- Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only)
- To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
- Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
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- Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%).
- Creatinine clearance ≥30 mL/min to <45 mL/min.
- Moderate hepatic impairment with total bilirubin >1.5 to .3.0 x upper limit of normal (ULN)
- ECOG performance status of 2 or 3
- Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status </=2 (unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5e above)
- Adequate renal function including creatinine < 1.5, unless related to the disease or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5c above.
- Adequate hepatic function (direct bilirubin < 2x upper limit of normal (ULN) unless increase is due to Gilbert fs disease or leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible, or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5d above)
- In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
- Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
- Willing and able to provide informed consent.
Who cannot join
- Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML).
- Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
- Participants with active, uncontrolled leukemia involvement of the CNS
- Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant including active cGVHD requiring topic therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to start of study treatment.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
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- Participant has a white blood cell count > 25 x 10^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.)
- 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.
- 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).
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Jacqueline Garcia, MD, 617-632-6349, jacqueline_garcia@dfci.harvard.edu
Jacqueline Garcia, MD
- Recruiting
Roswell Park
Buffalo, New York, 14263
Eunice Wang, MD, eunice.wang@roswellpark.org
Eunice Wang, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Courtney DiNardo, MD, 713-794-1141, cdinardo@mdanderson.org
Courtney DiNardo, MD
- Recruiting
University of Miami
Miami, Florida, 33136
Justin Watts, MD, 305-243-8986, jxw401@med.miami.edu
Justin Watts, MD
- Recruiting
The University of Kansas Medical Center
Westwood, Kansas, 66205
Yacoub Abdulraheem, MD, ayacoub@kumc.edu
Yacoub Abdulraheem, MD
About this study
To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.
Read the detailed description
Primary Objectives
- Phase 1b: To determine the safety and tolerability and recommended phase 2 dose (RP2D) of decitabine (either IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib.
- Phase 2: To determine the composite remission rate (CR, CRh and CRi) of decitabine (IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib for newly diagnosed (Arm A) or relapsed/refractory (Arm B) participants with IDH1-mutated myeloid malignancy.
Secondary Objectives
- To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS)
- To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.
- To determine the overall response rate (CR, CRh, CRi, MLFS, and PR)
- To characterize the pharmacokinetic (PK) profiles of venetoclax and olutasidenib in plasma samples (Phase 1b only).
Exploratory Objectives
- To investigate global gene expression profiles, DNA methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.
- Conditions
- Mutant IDH1 Inhibitor Olutasidenib
- Being tested
- Olutasidenib, Venetoclax, Decitabine, Decitabine/cedazuridine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlutasidenibDrug
Given by PO
VenetoclaxDrug
Also called ABT-199, GDC-0199
Given by PO
DecitabineDrug
Also called Dacogen
Given by IV
Decitabine/cedazuridineDrug
Also called INQOVI, ASTX727
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Participants enrolled in Part 1, the dose of venetoclax/decitabine you receive will depend on when you join this study. Up to 3 dose levels will be tested. Up to 6 participants will be enrolled at each dose level.
- All participants will receive the same dose level of olutasidenib. Receives: Drug: Olutasidenib; Drug: Venetoclax; Drug: Decitabine; Drug: Decitabine/cedazuridine |
| Part 2 | Experimental | Participants enrolled in Part 2, you will receive venetoclax/decitabine at the recommended dose that was found in Part 1.
- All participants will receive the same dose level of olutasidenib. Receives: Drug: Olutasidenib; Drug: Venetoclax; Drug: Decitabine; Drug: Decitabine/cedazuridine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start29 Aug 2024
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mutant IDH1 Inhibitor OlutasidenibStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rigel Pharmaceuticals,Inc.
- Responsible party
- Sponsor
- Investigators
- Courtney DiNardo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06445959
- Sponsor's protocol ID
- 2024-0180
- Other IDs
- NCI-2024-04807
- Status last verified
- Sep 2026
- First submitted
- 31 May 2024
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib
- ClinicalTrials.gov ID
- NCT06445959
- Acronym / sponsor ID
- 2024-0180
- Conditions
- Mutant IDH1 Inhibitor Olutasidenib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Rigel Pharmaceuticals,Inc.
- Study start
- 29 Aug 2024 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 6 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.
Detailed description
Primary Objectives
- Phase 1b: To determine the safety and tolerability and recommended phase 2 dose (RP2D) of decitabine (either IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib.
- Phase 2: To determine the composite remission rate (CR, CRh and CRi) of decitabine (IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib for newly diagnosed (Arm A) or relapsed/refractory (Arm B) participants with IDH1-mutated myeloid malignancy.
Secondary Objectives
- To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS)
- To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.
- To determine the overall response rate (CR, CRh, CRi, MLFS, and PR)
- To characterize the pharmacokinetic (PK) profiles of venetoclax and olutasidenib in plasma samples (Phase 1b only).
Exploratory Objectives
- To investigate global gene expression profiles, DNA methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Olutasidenib, Drug: Venetoclax, Drug: Decitabine, Drug: Decitabine/cedazuridineParticipants enrolled in Part 1, the dose of venetoclax/decitabine you receive will depend on when you join this study. Up to 3 dose levels will be tested. Up to 6 participants will be enrolled at each dose level. - All participants will receive the same dose level of olutasidenib. |
| Part 2 | Experimental | Drug: Olutasidenib, Drug: Venetoclax, Drug: Decitabine, Drug: Decitabine/cedazuridineParticipants enrolled in Part 2, you will receive venetoclax/decitabine at the recommended dose that was found in Part 1. - All participants will receive the same dose level of olutasidenib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age > 18 years
- Participants must have a documented IDH1 gene mutation
- Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR
- Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only)
- To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
Key exclusion criteria (9 listed)
- Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML).
- Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
- Participants with active, uncontrolled leukemia involvement of the CNS
- Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant including active cGVHD requiring topic therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to start of study treatment.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlutasidenibGiven by PO | Drug | Part 1, Part 2 |
| VenetoclaxAlso: ABT-199, GDC-0199Given by PO | Drug | Part 1, Part 2 |
| DecitabineAlso: DacogenGiven by IV | Drug | Part 1, Part 2 |
| Decitabine/cedazuridineAlso: INQOVI, ASTX727Given by PO | Drug | Part 1, Part 2 |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
Related trials for Mutant IDH1 Inhibitor Olutasidenib
Not yet recruitingPhase 2
Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; in High-Risk MDS Added to ASTX727; and Alone in Low Risk MDS (A MyeloMATCH Treatment Substudy)
Acute Myeloid Leukemia, Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Courtney DiNardo, MD principal investigator
M.D. Anderson Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Olutasidenib, Venetoclax and Decitabine in people with Mutant IDH1 Inhibitor Olutasidenib, run by M.D. Anderson Cancer Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Courtney DiNardo, MD ((713) 794-1141, cdinardo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.