High Grade Myelodysplastic SyndromesPhase 1/2NCT03564873
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
A Phase 1/2 study testing Omacetaxine and Azacitidine in people with High Grade Myelodysplastic Syndromes, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study will treat patients with previously untreated high grade myleodysplastic syndromes (MDS) with both omacetaxine mepesuccinate and azacitidine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Grade Myelodysplastic Syndromes
- What is being tested?
- Omacetaxine and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Sep 2018to Jun 2027
- Phase
- Phase 1/2
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
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Universtiy of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Concomitant Omacetaxine Mepesuccinate and Azacitidine for Patients With Previously Untreated High Grade Myelodysplastic Syndromes
This study will treat patients with previously untreated high grade myleodysplastic syndromes (MDS) with both omacetaxine mepesuccinate and azacitidine.
Read the detailed description
This is an open-label, phase I/II study for previously untreated patients with high grade MDS using omacetaxine and azacitidine with a small expansion cohort for relapsed and refractory MDS patients. Phase I features dose escalation, where patients will be assigned to one of three cohorts to receive different doses of omacetaxine with the standard dose and schedule of azacitidine, over a 28 day cycle. Phase II features the maximum tolerated dose from the Phase 1 study. An additional expansion cohort of 10 MDS patients who have failed to respond to or responded and relapsed after at least one line of therapy containing a hypomethylating agent therapy will also be accrued.
- Conditions
- High Grade Myelodysplastic Syndromes
- Being tested
- Omacetaxine, Azacitidine
- Keywords
- Omacetaxine, Azacitidine, Previously Untreated, Phase I/II, Dose Escalation, Maximum Tolerated Dose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmacetaxineDrug
Also called Phase 1
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.
AzacitidineDrug
Also called Phase 1
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.
OmacetaxineDrug
Also called Phase 2
Phase II is a maximum tolerated dose phase. Phase I will determine the maximum tolerated dose (highest amount that can be safely administered). Patients will receive omacetaxine subcutaneously at the maximum tolerated dose (0.5, 0.75, 1.0, or 1.25 mg/m2) twice daily on days 1 to 7.
AzacitidineDrug
Also called Phase 2
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Omacetaxine; Drug: Azacitidine |
| Cohort 5: Relapse Phase | Experimental | Not described Receives: Drug: Omacetaxine; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Study start date to study end date, or death, whichever comes first, up to 4 years.
Secondary outcomes (3)
Overall Survival
Measured: Study start date to study end date, or death, whichever comes first, up to 4 years.
Progression Free Survival
Progression Free Survival will be defined as the amount of time from administration of the initial dose of omacetaxine and azacitidine that a patient lives with the disease but does not get worse. This will be measured using Kaplan-Meier survival analysis curves.
Measured: Study start date to study end date, or death, whichever comes first, up to 4 years.
Duration of Response
Duration of Response will be defined as Time from documentation of tumor response to disease progression.This will be measured using Kaplan-Meier survival analysis curves.
Measured: Study start date to study end date, or death, whichever comes first, up to 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2018
- Study start17 Sep 2018
- Primary completion7 Oct 2025
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High Grade Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Pollyea, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03564873
- Sponsor's protocol ID
- 17-2215.cc
- Status last verified
- Sep 2026
- First submitted
- 8 Jun 2018
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 41140451