Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS

NCT03564873 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-2215.cc
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This study will treat patients with previously untreated high grade myleodysplastic syndromes (MDS) with both omacetaxine mepesuccinate and azacitidine.

Conditions

High Grade Myelodysplastic Syndromes

Keywords

Omacetaxine; Azacitidine; Previously Untreated; Phase I/II; Dose Escalation; Maximum Tolerated Dose

Outcome Measures

Primary Outcomes (2)

• Number of Participants Without Dose Limiting Toxicities in Cycle 1 for Phase 1 (Dose Escalation) Cohorts 0 and 1 to Determine Maximum Tolerated Dose

  Determine the recommended dose of omacetaxine based on the maximum tolerated dose. The MTD is defined as the highest dose at which ≤1 patient experiences a DLT in Cycle 1. Count of participants who did not experience a DLT are listed in outcome measure data table.

  Start of study through end of Cycle 1 (28 days) only for dose escalation cohorts

• Overall Response Rate

  This was a pre-specified primary outcome measure defined by the proportion of patients who achieve any category of complete remission (CR, includes CR and marrow CR) or partial remission (PR) based on the 2006 International Working Group (IWG) criteria for MDS1.

  Study start date to study end date, or death, whichever comes first, up to 4 years.

Secondary Outcomes (3)

• Overall Survival

  Study start date to study end date, or death, whichever comes first, up to 4 years.

• Progression Free Survival

  Study start date to study end date, or death, whichever comes first, up to 4 years.

• Duration of Response

  Study start date to study end date, or death, whichever comes first, up to 4 years.

Study Arms (6)

Cohort 0: De-Escalation Omacetaxine .5mg/m2

EXPERIMENTAL

De-escalation dose if DLTs are experienced for Cohort 1. Dose is Omacetaxine .5mg/m2 subcutaneous BID days 1-7.

Drug: Omacetaxine; Drug: Azacitidine

Cohort 1: Escalation Phase Omacetaxine .75mg/m2

EXPERIMENTAL

Patients in Cohort 1 will receive .75mg/m2 subcutaneous BID days 1-7.

Drug: Omacetaxine; Drug: Azacitidine

Cohort 2: Escalation Phase Omacetaxine 1.0mg/m2

EXPERIMENTAL

Patients in Cohort 2 will receive 1.0mg/m2 subcutaneous BID days 1-7.

Drug: Omacetaxine; Drug: Azacitidine

Cohort 3: Escalation Phase Omacetaxine 1.25mg/m2

EXPERIMENTAL

Patients in Cohort 3 will receive 1.25mg/m2 subcutaneous BID days 1-7.

Drug: Omacetaxine; Drug: Azacitidine

Cohort 4: Expansion Phase Omacetaxine .5mg/m2

EXPERIMENTAL

Dosing in Expansion Phase is based on the MTD determined with Cohorts 0-3. MTD was determined to be .5 mg/m2. Patients received .5mg/m2 Omacetaxine BID subcutaneously days 1-7.

Drug: Omacetaxine; Drug: Azacitidine

Cohort 5: Relapse Phase

EXPERIMENTAL

Drug: Omacetaxine; Drug: Azacitidine

Interventions

Omacetaxine DRUG

Phase I is a dose escalation phase. Patients will be enrolled into one of three cohorts to receive omacetaxine subcutaneously (0.5, 0.75, 1.0, or 1.25 mg/m2) twice daily on days 1 to 7.

Also known as: Phase 1

Cohort 0: De-Escalation Omacetaxine .5mg/m2; Cohort 1: Escalation Phase Omacetaxine .75mg/m2; Cohort 2: Escalation Phase Omacetaxine 1.0mg/m2; Cohort 3: Escalation Phase Omacetaxine 1.25mg/m2

Azacitidine DRUG

Azacitidine will be given at the standard dose and schedule, 75 mg/m2 once daily, on days 1 to 7. The patients will then be monitored for 21 more days ( to complete one 28 day cycle) but no more medication will be administered during those 21 days.

Also known as: Phase 1

Cohort 0: De-Escalation Omacetaxine .5mg/m2; Cohort 1: Escalation Phase Omacetaxine .75mg/m2; Cohort 2: Escalation Phase Omacetaxine 1.0mg/m2; Cohort 3: Escalation Phase Omacetaxine 1.25mg/m2

Eligibility Criteria

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

You may qualify if:

• A subject will be eligible for study participation if he/she meets the following criteria within 14 days prior to the first day of therapy (bone marrow biopsy can be performed 28 days prior to the first day of therapy).
• Subject must have confirmation of high grade MDS (MDS with excess blasts by WHO criteria) or chronic myelomonocytic leukemia with greater than 5% bone marrow blasts
• Subjects in the newly-diagnosed Phase 2 cohort must have received no prior treatment with a hypomethylating agent for MDS. Subjects in the relapsed/refractory Phase 2 cohort must have received at least 1 prior line of an HMA-containing regimen. "Refractory" is defined as having received at least four cycles of any HMA or HMA-containing regimen with \>5-19% bone marrow blasts. "Relapsed" is defined as having \>5-19% bone marrow blasts after having achieved a morphologic remission (≤5% bone marrow blasts) after at least one cycle of any HMA or HMA-containing regimen.
• Subject must be ≥ 18 years of age
• Subject must have a projected life expectancy of at least 12 weeks
• Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
• Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
• Subject must have adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 3.0 × ULN
• alanine aminotransferase (ALT) ≤ 3.0 × ULN
• direct bilirubin ≤ 3.0 × ULN
• Non-sterile male subjects must use contraceptive methods with partner(s) from time of enrollment and continuing up to 90 das after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
• Female subjects must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting omacetaxine; 2) throughout the entire duration of omacetaxine treatment; 3) during dose interruptions; and 4) for at least 90 days after omacetaxine discontinuation.
• Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

You may not qualify if:

• A subject will not be eligible for study participation if he/she meets any of the following criteria:
• Subject is known to be positive for HIV. HIV testing is not required.
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate.
• Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
• New York Heart Association heart failure \> class 2
• Renal, neurologic, psychiatric, endocrine, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia
• Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Patients on antibiotics with controlled systemic symptoms will not be excluded.
• Subject has uncontrolled diabetes
• Subject has had a recent major hemorrhage or has a bleeding diathesis associated with a high risk of bleeding
• Pregnant and breastfeeding females.
• Subject has a history of other malignancies prior to study entry, except for:
• Adequately treated in situ carcinoma of the breast or cervix uteri
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
• Prostate cancer with no plans for therapy of any kind
• Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Universtiy of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Pollyea DA, Stevens BM, Abbott D, Amaya M, Gutman JA, Kent A, McMahon C, Schwartz M, Smith C, Dell-Martin J, Sohalski C, Ellis A, Haag M, Schowinsky J, Pan Z, Patel SB, Ransom M, Gillen A, Jordan CT, Pietras EM. Omacetaxine and azacitidine for untreated patients with myelodysplastic syndromes and excess blasts: a phase I/II clinical trial. EClinicalMedicine. 2025 Oct 10;89:103546. doi: 10.1016/j.eclinm.2025.103546. eCollection 2025 Nov.

  PMID: 41140451 DERIVED

MeSH Terms

Interventions

Homoharringtonine; Clinical Trials, Phase I as Topic; Azacitidine; Clinical Trials, Phase II as Topic

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Daniel Pollyea
• Organization: University of Colorado

DANIEL.POLLYEA@CUANSCHUTZ.EDU

3037249562

Study Officials

• Daniel Pollyea, MD

  University of Colorado, Denver

  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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 21, 2018
• Study Start: September 17, 2018
• Primary Completion: October 7, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 29, 2026
• Results First Posted: September 29, 2026

Record last verified: 2026-09

Locations

US (1)