Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib

NCT06445959 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0180NCI-2024-04807
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.

Conditions

Mutant IDH1 Inhibitor Olutasidenib

Outcome Measures

Primary Outcomes (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

  Through study completion; an average of 1 year.

Study Arms (2)

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.

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.

Drug: Olutasidenib; Drug: Venetoclax; Drug: Decitabine; Drug: Decitabine/cedazuridine

Interventions

Olutasidenib DRUG

Given by PO

Part 1; Part 2

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Part 1; Part 2

Decitabine DRUG

Given by IV

Also known as: Dacogen

Part 1; Part 2

Decitabine/cedazuridine DRUG

Given by PO

Also known as: INQOVI, ASTX727

Part 1; Part 2

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Rigel Pharmaceuticals,Inc.: collaborator

Study Sites (2)

Roswell Park

Buffalo, New York, 14263, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

olutasidenib; venetoclax; Decitabine; decitabine and cedazuridine drug combination

Intervention Hierarchy (Ancestors)

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

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney DiNardo, MD

CONTACT

(713) 794-1141; cdinardo@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: August 29, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (2)