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

NCT07471841 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-AML24-687
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

IDH1 Mutation; Relapsed / Refractory AML

Outcome Measures

Primary Outcomes (1)

• Composite complete remission rate

  Composite complete remission (CRc) rate is defined as patients that meet the criteria for CR + CRh + CRi per the modified European LeukemiaNet (mELN) 2022. * Complete Remission (CR) is defined as absence of leukemia cells in the bone marrow (\< 5% blasts), normal blood counts (absolute neutrophil count ≥ 1000/μL and platelet count ≥ 100,000/μL), and the absence of circulating blasts, and extramedullary disease * Complete Remission with Hematologic recovery (CRh) is defined as meeting all criteria for CR as Bone marrow myeloblasts \< 5%; absence of circulating blasts; absence of extramedullary disease; both ANC ≥ 0.5x109/L (500/µL) and platelet count ≥ 50×109/L (50 000/µL) * Complete Remission with Incomplete hematologic recovery (CRi) is defined as meeting all criteria for Complete Remission (CR) except for either a low neutrophil count (neutropenia) or a low platelet count (thrombocytopenia)

  2 years

Secondary Outcomes (8)

• Overall response rate (ORR)

  2 years

• Overall survival

  2 years

• Duration of response (DoR)

  2 years

• Time to hematologic improvement (hemoglobin)

  2 years

• Time to hematologic improvement (platelet count)

  2 years

Study Arms (1)

Olutasidenib and Azacitidine

EXPERIMENTAL

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 or for whom loss of response is suspected. Subjects with at least a PR after 6 cycles of treatment will continue treatment.. Subjects without at least a PR after 6 cycles of treatment will move to long term follow up.

Drug: Olutasidenib; Drug: Azacitidine (AZA)

Interventions

Azacitidine (AZA) DRUG

Azacitidine 75 mg/m2 subcutaneously or IV (over 10-40 minutes)

Olutasidenib and Azacitidine

Olutasidenib DRUG

Olutasidenib 150 mg orally twice a day

Olutasidenib and Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 2 within 28 days prior to registration.
• 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)
• Acute Myeloid Leukemia with a documented IDH1 mutation.
• No more than 2 lines of prior therapy. NOTE: One line of therapy must have contained venetoclax.
• Persisting, non-hematologic and non-infectious toxicities from prior treatment must be Grade ≤ 2. NOTE: Documentation of these criteria is required at screening.
• 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
• Participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment.

You may not qualify if:

• Previous exposure to ivosidenib or any IDH1 inhibitor.
• 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.
• Known CNS involvement with AML.
• Previous allogeneic stem cell transplant within 60 days prior to registration.
• Treatment with any investigational drug within 21 days or 2 half-life's prior to registration.
• History of severe allergic anaphylactic reactions to olutasidenib or any of their excipients.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the subject is being treated on study.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Timothy Pardee: lead
• Atrium Health Wake Forest Baptist: collaborator
• Rigel Pharmaceuticals: collaborator

Study Sites (1)

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

olutasidenib; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Timothy Pardee, MD, PhD

  Atrium Health Wake Forest Baptist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy Pardee

CONTACT

MD, PhD; Timothy.Pardee@wfusm.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsr-investigator

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 13, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

US (1)