Acute Myeloid LeukemiaPhase 1NCT06514261
Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML
A Phase 1 study testing Azacitidine, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 4 sites in United States.
Trial summary
This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not received treatment (treatment naive). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine, Biospecimen Collection and Bone Marrow Aspiration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 4 sitesUnited States
- Study dates
- 18 Dec 2024to 16 Sep 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 must have established and confirmed diagnosis of intermediate or adverse-risk AML according to the European LeukemiaNet 2022 classification criteria
- Previously untreated AML excluding hydroxyurea and all-trans retinoic acid (ATRA). ATRA would only be used for suspected AML
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with venetoclax and azacitidine in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Patient is able to swallow oral medications
- Patient must have a body weight of at least 50 kg due to the use of flat doses
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- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN or ≤ 3 x ULN if patient has Gilbert's disease
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × institutional ULN or < 5 ULN if due to AML
- Chronic kidney disease (CKD)-epidemiology collaboration (EPI) glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m^2
- Peripheral white blood cell (WBC) count < 25 x 10^9/L on day 1 prior to treatment initiation. Hydroxyurea for up to 2 weeks is allowed for cytoreduction until 24 hours prior to study treatment
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better. Patients with a troponin leak (i.e. elevated troponin levels at presentation without evidence of an active myocardial infarction (MI) are eligible
- The effects of iadademstat on the developing human fetus are unknown. For this reason and because LSD1 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 180 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males with female partners of child-bearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 180 days after the last dose of study medication. Women of child-bearing potential agree not to donate or freeze egg(s) during the course of this study or within 180 days after receiving their last dose of study drug. Male patients agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug
- Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Who cannot join
- Patients are willing and able to receive intensive induction chemotherapy
- Patients have isolated myeloid sarcoma or acute promyelocytic leukemia (APL) French-American-British (FAB) M3
- Patients who have not recovered from adverse events of grade 3 or more due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients who have active central nervous system (CNS) involvement by AML
- Patients who have disseminated intravascular coagulopathy with active systemic bleeding or venous or atrial signs of thrombosis
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- Patients who require treatment while on study with concomitant drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline) except for drugs that are considered absolutely essential for the care of the patient and with appropriate treatment monitoring
- Patients with manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of oral drugs. In addition, patients with enteric stomata are also excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to iadademstat, azacitidine, mannitol, or venetoclax
- Iadademstat Concomitant Medication Considerations: Patients are not allowed to receive prophylactic hematopoietic colony stimulating factors, any complementary or alternative medicine (any of various systems of healing or treating disease [as non-prescription drugs, herbal medicine and homeopathy])
- Patients should not use strong CYP3A inhibitors with the exception of antifungals for which standard of care (SOC) dose modifications of venetoclax exist
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous. This includes, but is not limited to:
- Myocardial infarction with evidence of residual abnormalities within 3 months prior to enrollment (Troponin leak alone not included if no residual dysfunction);
- New York Heart Association (NYHA) Class III or IV heart failure;
- Severe uncontrolled ventricular arrhythmias;
- Electrocardiographic evidence of acute ischemia or active life-threatening conduction system abnormalities:
- Since patients with AML frequently require supportive care with agents that affect the corrected QT interval (QTc), if clinically indicated, obtain an electrocardiogram (ECG) prior to enrollment
- As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control (i.e., no signs of severe systemic inflammatory response that makes patient clinically unstable in the opinion of the investigator, and the patient is hemodynamically stable). Patients with uncontrolled infection shall not be enrolled until the infection is treated and brought under control
- Pregnant women are excluded from this study because iadademstat is LSD1 inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iadademstat, breastfeeding should be discontinued if the mother is treated with iadademstat. These potential risks may also apply to other agents used in this study
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML
This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not received treatment (treatment naive). Chemotherapy drugs, such as iadademstat and azacitidine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the recommended phase 2 dose (RP2D) and safety profile of iadademstat in combination with venetoclax and azacitidine.
SECONDARY OBJECTIVES:
- To observe and record anti-tumor activity, including evaluating the overall response rate (ORR), defined as complete remission (CR), CR with incomplete hematologic recovery (Cri), or CR with partial hematologic recovery (CRh).
II. To evaluate the measurable residual disease (MRD)-negative composite CR (cCR) rate after 1, 2, and 3 cycles using multiparameter flow cytometry (MFC) and evaluate event-free survival (EFS), overall survival (OS), and duration of response (DoR).
III. To determine if treatment will be associated with expansion of high risk molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) markers over time.
EXPLORATORY OBJECTIVES:
- To determine the rate of MRD-negative cCR across molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) subgroups.
II. To document the effect of therapy on LSD1-target engagement.
III. To determine if secondary resistance (remission with therapy then relapse) in both arms is associated with:
IIIa. Acquisition of resistance mutations including BCL-2 and BAX; IIIb. Development or expansion of mutations that activate RAS/MAPK/FLT3 including NRAS, KRAS, PTPN11, NF1, and FLT3-ITD; IIIc. Over-expression of resistance proteins such as MCL-1 or BCL-XL. IV. To determine pharmacokinetics (PK) in the triplet therapy of iadademstat, azacitidine, and venetoclax.
- To explore PK/pharmacodynamic (PD) relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat, azacitidine, and venetoclax.
VI. To evaluate the association between time to achieve an MRD-negative cCR and EFS, OS, and DoR.
OUTLINE: This is a dose-escalation study of iadademstat and venetoclax in combination with azacitidine.
INDUCTION: Patients receive iadademstat orally (PO) once daily (QD) on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study.
CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.
After completion of study treatment, patients are followed every 3-4 months for up to 2 years.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine, Biospecimen Collection, Bone Marrow Aspiration, Buccal Swab, Iadademstat
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine
Given IV or SC
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood samples
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Buccal SwabProcedure or surgery
Also called Buccal Scraping, Buccal Smear, Buccal swab/scraping, Buccal Swabbing
Undergo buccal swab
IadademstatDrug
Also called ORY 1001, ORY-1001, RG 6016, RG6016
Given PO
VenetoclaxDrug
Also called ABT 199, ABT-0199, ABT-199, ABT199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (iadademstat, venetoclax, azacitidine) | Experimental | INDUCTION: Patients receive iadademstat PO QD on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study.
CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study. Receives: Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Buccal Swab; Drug: Iadademstat; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicity (DLT)
DLT will be defined as any of the following adverse events (AEs) that cannot be considered primarily related to the underlying acute myeloid leukemia or a comorbid condition and evaluated during the first cycle of treatment. Will utilize National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for toxicity grading and reporting.
Measured: Up to completion of cycle 1
Incidence of AEs
Will utilize NCI-CTCAE v5.0 for AE grading and reporting.
Measured: Up to completion of therapy
Secondary outcomes (7)
Objective response rate
The probability of achieving a complete remission (CR), CR with incomplete hematologic recovery (CRi), CR with partial hematologic recovery (CRh), will be estimated with exact 95% binomial confidence intervals.
Measured: Up to 4 years
Morphologic leukemia free state
Measured: Up to 4 years
Minimal residual disease (MRD)-negative composite complete remission (cCR)
Will be estimated with exact 95% binomial confidence intervals.
Measured: After completion of 2 cycles
Event free survival
Will be estimated by the Kaplan-Meier method, along with 95% confidence regions.
Measured: From study enrollment to disease progression, treatment failure (failure to achieve CR or < 5% bone marrow blasts) confirmed relapse or death, up to 4 years
Overall survival
Will be estimated by the Kaplan-Meier method, along with 95% confidence regions.
Measured: Up to 4 years
Duration of response
Will be estimated by the Kaplan-Meier method, along with 95% confidence regions.
Measured: Up to 4 years
Proportion of patients with high risk molecular and cytogenetic markers
Will be estimated with exact 95% binomial confidence intervals and compared between baseline, during treatment, and at progression of disease.
Measured: At baseline, during treatment, and at progression of disease, 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 posted23 Jul 2024
- Study start18 Dec 2024
- Primary completion16 Sep 2027 (estimated)
- Study completion16 Sep 2027 (estimated)
Why it stopped: Other - Pending amendment for study expansion.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Annie P Im, Principal investigator, University of Pittsburgh Cancer Institute LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06514261
- Sponsor's protocol ID
- NCI-2024-04616
- Other IDs
- NCI-2024-04616, 24-115, 10630, 10630, UM1CA186690
- Status last verified
- Aug 2026
- First submitted
- 20 Jul 2024
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML
- ClinicalTrials.gov ID
- NCT06514261
- Acronym / sponsor ID
- NCI-2024-04616
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Other - Pending amendment for study expansion.
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 18 Dec 2024 (actual)
- Primary completion
- 16 Sep 2027 (estimated)
- Study completion
- 16 Sep 2027 (estimated)
- First posted
- 23 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not received treatment (treatment naive). Chemotherapy drugs, such as iadademstat and azacitidine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML.
Detailed description
PRIMARY OBJECTIVE:
- To determine the recommended phase 2 dose (RP2D) and safety profile of iadademstat in combination with venetoclax and azacitidine.
SECONDARY OBJECTIVES:
- To observe and record anti-tumor activity, including evaluating the overall response rate (ORR), defined as complete remission (CR), CR with incomplete hematologic recovery (Cri), or CR with partial hematologic recovery (CRh).
II. To evaluate the measurable residual disease (MRD)-negative composite CR (cCR) rate after 1, 2, and 3 cycles using multiparameter flow cytometry (MFC) and evaluate event-free survival (EFS), overall survival (OS), and duration of response (DoR).
III. To determine if treatment will be associated with expansion of high risk molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) markers over time.
EXPLORATORY OBJECTIVES:
- To determine the rate of MRD-negative cCR across molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) subgroups.
II. To document the effect of therapy on LSD1-target engagement.
III. To determine if secondary resistance (remission with therapy then relapse) in both arms is associated with:
IIIa. Acquisition of resistance mutations including BCL-2 and BAX; IIIb. Development or expansion of mutations that activate RAS/MAPK/FLT3 including NRAS, KRAS, PTPN11, NF1, and FLT3-ITD; IIIc. Over-expression of resistance proteins such as MCL-1 or BCL-XL. IV. To determine pharmacokinetics (PK) in the triplet therapy of iadademstat, azacitidine, and venetoclax.
- To explore PK/pharmacodynamic (PD) relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat, azacitidine, and venetoclax.
VI. To evaluate the association between time to achieve an MRD-negative cCR and EFS, OS, and DoR.
OUTLINE: This is a dose-escalation study of iadademstat and venetoclax in combination with azacitidine.
INDUCTION: Patients receive iadademstat orally (PO) once daily (QD) on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study.
CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.
After completion of study treatment, patients are followed every 3-4 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (iadademstat, venetoclax, azacitidine) | Experimental | Drug: Azacitidine, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Buccal Swab, Drug: Iadademstat, Drug: VenetoclaxINDUCTION: Patients receive iadademstat PO QD on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study. CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have established and confirmed diagnosis of intermediate or adverse-risk AML according to the European LeukemiaNet 2022 classification criteria
- Previously untreated AML excluding hydroxyurea and all-trans retinoic acid (ATRA). ATRA would only be used for suspected AML
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with venetoclax and azacitidine in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Patient is able to swallow oral medications
Key exclusion criteria (19 listed)
- Patients are willing and able to receive intensive induction chemotherapy
- Patients have isolated myeloid sarcoma or acute promyelocytic leukemia (APL) French-American-British (FAB) M3
- Patients who have not recovered from adverse events of grade 3 or more due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients who have active central nervous system (CNS) involvement by AML
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacitidine, 5-AzacytidineGiven IV or SC | Drug | Treatment (iadademstat, venetoclax, azacitidine) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo collection of blood samples | Procedure or surgery | Treatment (iadademstat, venetoclax, azacitidine) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (iadademstat, venetoclax, azacitidine) |
| Bone Marrow AspirationUndergo bone marrow aspiration | Procedure or surgery | Treatment (iadademstat, venetoclax, azacitidine) |
| Buccal SwabAlso: Buccal Scraping, Buccal Smear, Buccal swab/scraping, Buccal SwabbingUndergo buccal swab | Procedure or surgery | Treatment (iadademstat, venetoclax, azacitidine) |
| IadademstatAlso: ORY 1001, ORY-1001, RG 6016, RG6016Given PO | Drug | Treatment (iadademstat, venetoclax, azacitidine) |
| VenetoclaxAlso: ABT 199, ABT-0199, ABT-199, ABT199Given PO | Drug | Treatment (iadademstat, venetoclax, azacitidine) |
Primary outcome
Incidence of dose limiting toxicity (DLT)
Time frame: Up to completion of cycle 1
DLT will be defined as any of the following adverse events (AEs) that cannot be considered primarily related to the underlying acute myeloid leukemia or a comorbid condition and evaluated during the first cycle of treatment. Will utilize National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for toxicity grading and reporting.
Incidence of AEs
Time frame: Up to completion of therapy
Will utilize NCI-CTCAE v5.0 for AE grading and reporting.
7 secondary outcomes
Objective response rate
Time frame: Up to 4 years
Morphologic leukemia free state
Time frame: Up to 4 years
Minimal residual disease (MRD)-negative composite complete remission (cCR)
Time frame: After completion of 2 cycles
Event free survival
Time frame: From study enrollment to disease progression, treatment failure (failure to achieve CR or < 5% bone marrow blasts) confirmed relapse or death, up to 4 years
Overall survival
Time frame: Up to 4 years
Duration of response
Time frame: Up to 4 years
Proportion of patients with high risk molecular and cytogenetic markers
Time frame: At baseline, during treatment, and at progression of disease, up to 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annie P Im principal investigator
University of Pittsburgh Cancer Institute LAO
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicity (DLT) (time frame: Up to completion of cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.