Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1

NCT04874194 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2020-0890NCI-2021-03341
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial best dose, possible benefits and/or side effects of omacetaxine and venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has come back (recurrent) or does not respond to treatment (refractory) and have a genetic change RUNX1. Drugs used in chemotherapy, such as omacetaxine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving omacetaxine and venetoclax may help to control the disease.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Acute Biphenotypic Leukemia; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) of Omacetaxine in Combination With Venetoclax

  The RP2D will be selected at the end of the Phase 1b portion based on safety data , in Arms A and B independently. Preliminary efficacy and PK data for each dose level may also be considered as appropriate.

  Up to 30 days

• Number of Participant to Achieve Complete Remission

  Complete Remission for AML is defined as: Absolute neutrophil count \> 10\^3/UL, platelets . 10\^5/UL, red cell transfusion independence, absence of extramedullary disease, and bone marrow with \< 5% blasts. Complete Remission for MDS is defined as: Absolute neutrophil count \> 10\^3/UL, platelets . 10\^5/UL, hemoglobin \>11 g/dl, and bone marrow with \< 5% blasts. Peripheral dysplasia will be noted.

  At day 28, and 3 cycles.

Secondary Outcomes (3)

• Event-free Survival (EFS)

  Up to Two years, 8 months, 30 days

• Overall Survival (OS)

  Up to Two years, 8 months, 30 days

• Duration of Response

  Up to Two years, 8 months, 30 days

Study Arms (6)

Ph 1 Arm A (AML) Dose 0

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-10 . Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Ph 1 Arm B (MDS) Dose 0

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-10 . Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Ph 1 Arm A (AML) Dose +1

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Ph 1 Arm B (MDS) Dose + 1

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Ph 2 Arm A (AML) Dose +1

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Ph 2 Arm B (MDS) Dose + 1

EXPERIMENTAL

Participants receive omacetaxine SC BID on days 2-4, and venetoclax PO on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax

Interventions

Omacetaxine Mepesuccinate DRUG

Given SC

Also known as: Ceflatonin, Cephalotaxine, 4-methyl 2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (ester), [3(R)]- (9CI), CGX-635, HHT, homoharringtonine, Synribo

Ph 1 Arm A (AML) Dose +1; Ph 1 Arm A (AML) Dose 0; Ph 1 Arm B (MDS) Dose + 1; Ph 1 Arm B (MDS) Dose 0; Ph 2 Arm A (AML) Dose +1; Ph 2 Arm B (MDS) Dose + 1

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Ph 1 Arm A (AML) Dose +1; Ph 1 Arm A (AML) Dose 0; Ph 1 Arm B (MDS) Dose + 1; Ph 1 Arm B (MDS) Dose 0; Ph 2 Arm A (AML) Dose +1; Ph 2 Arm B (MDS) Dose + 1

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of relapsed or refractory acute myeloid leukemia (AML) (or biphenotypic or bilineage leukemia including a myeloid component) or myelodysplastic syndrome
• For myelodysplastic syndrome (MDS) patients, patients must have no response, progression, or relapse following at least 4 cycles of azacytidine or decitabine; and/or intolerance defined as grade \>= 3 drug-related toxicity precluding continued therapy
• Age \>= 18 years
• Subjects must have documented RUNX1 gene mutation
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Creatinine \< 2 unless related to the disease
• Direct bilirubin \< 2x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \< 3x ULN unless considered due to leukemic involvement
• 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 (i.e. immunotherapy) agents. Oral hydroxyurea and/or cytarabine (up to 2 g/m\^2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI)
• 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
• Willing and able to provide informed consent

You may not qualify if:

• Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
• Patients with any concurrent uncontrolled clinically significant medical condition including active infection or psychiatric illness, which could place the patient at unacceptable risk of study treatment
• 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)
• Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or known human immunodeficiency virus (HIV) infection
• Subject has a white blood cell count \> 25 x 10\^9/L. (Note: Hydroxyurea 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, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• DiNardo CD, Jen WY, Montalban-Bravo G, Wang X, Loghavi S, Lavu S, Short NJ, Chien K, Issa GC, Pemmaraju N, Yilmaz M, Andreeff M, Borthakur G, Kadia TM, Daver NG, Garcia-Manero G, Mill CP, Su X, Fiskus W, Bhalla KN. Omacetaxine and venetoclax in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome with mutant RUNX1. Blood Neoplasia. 2025 Jul 25;2(4):100145. doi: 10.1016/j.bneo.2025.100145. eCollection 2025 Nov.

  PMID: 40979071 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Homoharringtonine; Esters; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Courtney DiNardo MD, Professor
• Organization: The university of Texas MD Anderson Cancer Center

cdinardo@mdanderson.org

713-794-1141

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 1, 2021
• First Posted: May 5, 2021
• Study Start: December 17, 2021
• Primary Completion: September 16, 2024
• Study Completion: September 16, 2024
• Last Updated: November 3, 2025
• Results First Posted: November 3, 2025

Record last verified: 2025-10

Locations

US (1)