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AzTrials

Targeted TherapyPhase 2NCT07032727

Olutasidenib Combined With Co-targeted Therapy in Relapsed or Refractory IDH1-mutated Myeloid Malignancies Harboring Activated Signaling Pathway Mutations

A Phase 2 study testing Olutasidenib, Cladribine (CLAD) and Venetoclax in people with Targeted Therapy and IDH1-Mutated Malignancies, run by M.D. Anderson Cancer Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

To learn about the safety and tolerability of study drug combinations in patients with relapsed/refractory, IDH1-mutated myeloid malignancies with a co-signaling mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Olutasidenib, Cladribine (CLAD) and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
2 sitesUnited States
Study dates
12 Sep 2025to 1 Jun 2029
Phase
Phase 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 with a diagnosis of relapsed and/or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component) OR high-risk MDS, MPN, or MDS/MPN (defined as ≥10% blasts on peripheral flow cytometry or bone marrow biopsy).
  • Participants must have a documented IDH1 mutation.
  • Participants must also have a documented co-signaling mutation in one or more of the following: KRAS, NRAS, PTPN11, CBL, NF1, FLT3-ITD, FLT3-TKD, KIT, JAK2, MPL, CALR, CSF3R.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
  • Adequate renal function with estimated GFR ≥ 30 by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
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  • Adequate hepatic function, defined as direct bilirubin ≤ 2x upper limit of normal (ULN) and AST and ALT ≤ 3x ULN unless the increase is due to Gilbert's disease or leukemic involvement, in which case direct bilirubin, AST, and ALT ≤ 5x ULN will be considered eligible.
  • The interval from prior treatment to time of initiation will be at least 14 days OR five half-lives for both cytotoxic and non-cytotoxic (e.g. immunotherapy agent(s)). Oral hydroxyurea and/or cytarabine (up to 2g/m2) is allowed for participants with rapidly proliferative disease prior tothe start and during the first two cycles of therapy, for clinical benefit and after discussion with the PI. Continuation of concurrent intrathecal therapy for controlled CNS disease is permitted.
  • Ability to understand and the willingness to sign an informed consent document.

Who cannot join

  • Participants who have received prior olutasidenib (Rezlidhiai, previously FT-2102).
  • Participants with translocation t(15;17) or acute promyelocytic leukemia (French-American British (FAB) class M3-AML).
  • Participants with any concurrent uncontrolled clinically significant medical condition, including life threatening infection, which could place the patient at unacceptable risk of study treatment.
  • Participants with any uncontrolled psychiatric illness that would limit compliance with study requirements.
  • Participants with a New York Heart Association (NYHA) Functional Classification of III or IV.
  • Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant (Participants without active GVHD on phototherapy for chronic skin GVHD are permitted after discussion with the PI). Participants must have discontinued calcineurin inhibitors at least 4 weeks prior to the start of study treatment.
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  • Participants with active, uncontrolled CNS leukemia.
  • Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
  • Known active hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection. For participants with evidence of chronic HBV or HIV infection, the HBV or HIV viral load must be undetectable, respectively. For participants with a history of HCV, it must be treated and cured with an undetectable HCV viral load.
  • Participant has white blood cell count >25 x 109/L (Note: Hydroxyurea and cytarabine are permitted to mean this criterion).
  • The effects of the study drug on the developing human fetus or transmission through breast feeding are unknown. Therefore, nursing women and women with a positive urine pregnancy test and excluded. Additionally, women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP who are not willing to maintain adequate contraception are excluded.
  • WOCBP includes all female participants between the onset of menses (as early as 8 years of age) to 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: i. Postmenopausal (no menses in greater than or equal to 12 consecutive months).
  • History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
  • History of bilateral tubal ligation or another surgical sterilization procedure.
  • Approved methods of birth control are as follows: hormonal contraception (i.e. birth control pills, injection, transdermal patch, vaginal ring, hormonal implant), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post-vasectomy, double barrier methods (e.g. condom in combination with spermicide). Abstinence for the duration of the trial and drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately.
  • Adequate contraception must be maintained from initiation of the study drug until 90 days after the last dose of the study drug.
  • History of an allergic reaction to venetoclax, gilteritinib, ruxolitinib, cladribine, or cytarabine.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Courtney DiNardo, MD contact

713-794-1141

cdinardo@mdanderson.org

United States2 sites, 2 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

Other trials in United States

About this study

To learn about the safety and tolerability of study drug combinations in patients with relapsed/refractory, IDH1-mutated myeloid malignancies with a co-signaling mutation.

Read the detailed description

Primary Objectives

  1. To determine the safety and tolerability of olutasidenib in combination with cladribine + LDAC ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm 3) for patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation.
  2. To quantify the composite complete remission rate (CRc; CR + CRh + CRi) in patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation treated with olutasidenib in combination with cladribine + LDAC ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm3).

Secondary Objectives

  1. To determine overall survival (OS), event free survival (EFS), and duration of response (DOR) with olutasidenib in combination with a co-targeting chemotherapeutic agent.
  2. To determine the overall response rate (ORR; CR + CRh + CRi + MLFS + PR) of olutasidenib in combination with a co-targeting chemotherapeutic agent.
  3. To evaluate occurrence of measurable residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation by polymerase chain reaction (PCR) and next generation sequencing (NGS)-based assays (e.g. IDH1 and FLT3 if applicable).
  4. To characterize the pharmacokinetic (PK) profiles of olutasidenib and venetoclax in plasma samples.
Being tested
Olutasidenib, Cladribine (CLAD), Venetoclax, Gilteritinib, Ruxolitinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlutasidenibDrug

    Given by po

  • Cladribine (CLAD)Drug

    Given by IV

  • VenetoclaxDrug

    Given by po

  • GilteritinibDrug

    Given by po

  • RuxolitinibDrug

    Given by po

  • CytarabineDrug

    Given SQ

Study groups in NCT07032727
Study groupRoleWhat they receive
Arm 1A Safety Lead-In/Expansion:ExperimentalTreatment with Olutasidenib + Cladribine + Cytarabine
Receives: Drug: Olutasidenib; Drug: Cladribine (CLAD); Drug: Cytarabine
Arm 1B ExpansionExperimentalTreatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax
Receives: Drug: Olutasidenib; Drug: Cladribine (CLAD); Drug: Venetoclax; Drug: Cytarabine
Arm 2A Safety Lead-In/ExpansionExperimentalTreatment with Olutasidenib + Gilteritnib
Receives: Drug: Olutasidenib; Drug: Gilteritinib
Arm 2B ExpansionExperimentalTreatment with Olutasidenib + Gilteritnib + Venetoclax
Receives: Drug: Olutasidenib; Drug: Venetoclax; Drug: Gilteritinib
Arm 3A Safety Lead-In/Expansion:ExperimentalTreatment with Olutasidenib + Ruxolitinib
Receives: Drug: Olutasidenib; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

  1. First posted24 Jun 2025
  2. Study start12 Sep 2025
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Jun 2029 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
68 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07032727
Sponsor's protocol ID
2025-0520
Other IDs
NCI-2025-04331
Status last verified
Oct 2026
First submitted
16 Jun 2025
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olutasidenib, Cladribine (CLAD) and Venetoclax in people with Targeted Therapy and IDH1-Mutated Malignancies, run by M.D. Anderson Cancer Center at 2 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 9 inclusion and 17 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 2 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 phase mean?

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?

On the ClinicalTrials.gov record for NCT07032727.

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.

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