Hematopoietic and Lymphoid Cell NeoplasmPhase 1/2NCT04874194
Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1
A Phase 1/2 study testing Omacetaxine Mepesuccinate and Venetoclax in people with Hematopoietic and Lymphoid Cell Neoplasm and Recurrent Acute Biphenotypic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Recurrent Acute Biphenotypic Leukemia, Recurrent Acute Myeloid Leukemia
- What is being tested?
- Omacetaxine Mepesuccinate and Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2021to 16 Sep 2024
- 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
- 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
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- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib/II Study of Omacetaxine and Venetoclax for Patients With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety and tolerability and recommended phase 2 dose (RP2D) of omacetaxine in combination with venetoclax for patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome harboring a RUNX1 mutation. (Phase 1b) II. To determine the efficacy of omacetaxine in combination with venetoclax for patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome harboring a RUNX1 mutation. (Phase II)
SECONDARY OBJECTIVES:
- To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS).
II. To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.
OUTLINE: This is a phase I, dose de-escalation study followed by a phase II study.
Patients receive omacetaxine subcutaneously (SC) twice daily (BID) on days 2-3 or 2-4, and venetoclax orally (PO) on days 1-7, 1-10 or 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, then every 3 months for 3 years.
- 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
- Being tested
- Omacetaxine Mepesuccinate, Venetoclax
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omacetaxine MepesuccinateDrug
Also called Ceflatonin, Cephalotaxine, 4-methyl 2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (ester), [3(R)]- (9CI), CGX-635, HHT
Given SC
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Omacetaxine Mepesuccinate; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At day 28, and 3 cycles.
Secondary outcomes (3)
Event-free Survival (EFS)
Time from date of treatment start until the date of failure or death from any cause.
Measured: Up to Two years, 8 months, 30 days
Overall Survival (OS)
The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients in terms of OS.
Measured: Up to Two years, 8 months, 30 days
Duration of Response
Response date to loss of response or last follow up.
Measured: Up to Two years, 8 months, 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2021
- Study start17 Dec 2021
- Primary completion16 Sep 2024
- Study completion16 Sep 2024
Why it stopped: The study terminated early because the company was longer providing the investigational product.
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 Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Courtney DiNardo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04874194
- Sponsor's protocol ID
- 2020-0890
- Other IDs
- NCI-2021-03341, 2020-0890
- Status last verified
- Oct 2025
- First submitted
- 1 May 2021
- Last updated
- 3 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40979071