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Acute Myeloid LeukemiaPhase 1NCT06802523

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia

A Phase 1 study testing Actinium Ac 225 Lintuzumab, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of lintuzumab-Ac225 in combination with venetoclax and ASTX-727, and how well they work in treating patients with newly diagnosed acute myeloid leukemia (AML). 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?
Actinium Ac 225 Lintuzumab, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
18 Nov 2026to 31 Dec 2028
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 histologically or cytologically confirmed diagnosis of acute myeloid leukemia (AML) according to 2022 World Health Organization (WHO) criteria
  • Evidence of CD33 expression in more than 25% of bone marrow blasts by flow cytometry determined by local assessment
  • Patients must be considered ineligible for induction therapy defined by the following
  • ≥ 75 years of age; OR
  • <75 years of age with at least one of the following co-morbidities or high-risk genetic features. Geriatric assessment and other tools to assess frailty have not been validated in patients with AML, and therefore will not be used to assess eligibility
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3;
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  • Cardiac history of congestive heart failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina;
  • Diffusion capacity of lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%;
  • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × upper limit of normal (ULN)
  • Patents with high risk genetic features based on local testing
  • inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)
  • t(3q26.2;v)
  • -5 or del(5q); -7; -17/abnormal(17p)
  • Complex karyotype or monosomal karyotype as defined by ELN 2022
  • Mutated TP53
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of linituzumab-Ac-225 in combination with venetoclax and ASTX-727 in patients < 18 years of age, children are excluded from this study
  • ECOG performance status 0-3 (Karnofsky ≥ 60%). For patients with ECOG performance status of 3, the decline in status should be due to AML per investigator's determination
  • Total bilirubin ≤ 3.0x institutional ULN unless considered due to Gilbert syndrome
  • Aspartate aminotransferase (AST)(serum gluatmic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
  • Creatinine clearance ≥ 60 ml/min
  • 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 (NYHA) Functional Classification. Patients with heart failure must have NYHA functional class congestive heart failure (CHF) II or below to be eligible
  • Hydroxyurea, cytarabine or leukopheresis are allowed for management of hyperleukocytosis, before initiation of study therapy. All-trans retinoic acid (ATRA) given emergently for suspected acute promyelocytic leukemia (APL) is also allowed. White blood cell (WBC) count must be < 25 x 10^9/L to start on study therapy per venetoclax label. Hydroxyurea and ATRA may be administered up to one day prior to start of study treatment
  • 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

  • Acute promyelocytic leukemia (APL)
  • Patients with favorable risk AML per the European LeukemiaNet (ELN) 2022 criteria
  • Active central nervous system (CNS) involvement of AML requiring therapy
  • Prior therapy with radiopharmaceuticals or external beam radiation therapy (EBRT)
  • Previous therapy with venetoclax or other BCL-2 directed therapy
  • Patients with Fridericia-corrected QT interval (QTcF) > 450ms at screening. QTcF will be calculated as the mean of the QTcF value from three separate electrocardiography (EKGs)
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  • Receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or ASTX-727
  • Uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous per investigators opinion
  • Pregnant women are excluded from this study because lintuzumab-Ac225 is a radiotherapy agent 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 lintuzumab-Ac225, breastfeeding should be discontinued if the mother is treated with lintuzumab-Ac225. These potential risks may also apply to other agents used in this study
  • Women of child-bearing potential must agree to use adequate contraception (hormonal birth control or abstinence) prior to study entry and for the duration of study participation, and for 6 months following completion of study treatment. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception (latex or synthetic condom or abstinence) prior to the study, for the duration of study participation, and 3 months after completion of the study
  • Patients unable to swallow tablets/capsules and patients with malabsorption syndrome or other conditions that may interfere with the oral administration of medications are not eligible
  • Patients who have had chemotherapy, targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib, hydroxyurea, cytarabine or ATRA),within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study are not eligible
  • Prior allogenic stem cell transplant
  • Patients who received a live vaccine within 30 days of planned start of study therapy
  • NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist, registered trademark) are live attenuated vaccines, and are not allowed
  • Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment and are unwilling to discontinue consumption of these throughout the receipt of study drugs
  • Patients who are unable to take spironolactone or eplerenone due to intolerance, allergy, drug-drug interactions, or for any other reason

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale University Cancer Center LAO

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: A Phase I Study of Lintuzumab-Ac-225 in Combination With Venetoclax and ASTX-727 in Adults With Newly Diagnosed AML

This phase I trial tests the safety, side effects, and best dose of lintuzumab-Ac225 in combination with venetoclax and ASTX-727, and how well they work in treating patients with newly diagnosed acute myeloid leukemia (AML). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called actinium Ac 225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers actinium Ac 225 to kill them. 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. ASTX-727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving lintuzumab-Ac225 in combination with venetoclax and ASTX-727 may be safe and tolerable in treating patients with newly diagnosed AML and may improve the chance of going into remission and staying in remission for a longer period of time.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine recommended phase 2 dose (RP2D) of actinium Ac 225 lintuzumab (lintuzumab-Ac225) when used in combination with venetoclax and decitabine and cedazuridine (ASTX-727).

SECONDARY OBJECTIVES:

  1. To determine the maximum tolerated dose of lintuzumab-Ac225 when used in combination with venetoclax and ASTX-727.

II. To describe the frequency and severity of adverse events of patients treated on study, including cytopenia and organ toxicity after second dose of lintuzumab-Ac225.

III. To determine the rate and time to complete remission (CR), complete remission with incomplete hematologic recovery (Cri), and complete remission with partial hematologic recovery (CRh).

IV. To determine the rate and time to achieve CR/Cri/CRh without minimal residual disease (MRD) by multiparameter flow cytometry (MFC).

  1. To determine the duration of remission, event-free and overall survival of patients.

VI. To evaluate and compare the clinical activity and toxicity between two lintuzumab-Ac225 administration schedules.

EXPLORATORY OBJECTIVES:

  1. To correlate CD33 expression on AML cells with response to lintuzumab-Ac225 in combination with venetoclax and ASTX-727.

II. To evaluate CD33 isoforms as a variable for response to lintuzumab-Ac225 combination with venetoclax and ASTX-727.

OUTLINE: This is a dose-escalation study of lintuzumab-Ac225 in combination with venetoclax and ASTX-727. During dose-escalation phase, patients are randomized to 1 of 2 schedules.

SCHEDULE 1:

INDUCTION: Patients receive lintuzumab-Ac225 intravenously (IV) over 30 minutes on day 8, venetoclax orally (PO) once daily (QD) on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1.

RE-INDUCTION: Patients with CR, partial response (PR) or no response (NR) after cycle 1 receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2.

MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or morphologic leukemia-free state (MLFS) after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.

SCHEDULE 2:

INDUCTION: Patients receive lintuzumab-Ac225 V over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1.

RE-INDUCTION: Patients with CR, PR or NR receive lintuzumab-Ac225 IV over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2.

MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Being tested
Actinium Ac 225 Lintuzumab, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Decitabine and Cedazuridine
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.

  • Actinium Ac 225 LintuzumabRadiation

    Also called 225Ac-HuM195, Actimab-A, Actinium (225Ac) Lintuzumab Satetraxetan, Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195

    Given IV

  • 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 and biopsy

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow aspiration and biopsy

  • Decitabine and CedazuridineDrug

    Also called ASTX 727, ASTX-727, ASTX727, C-DEC

    Given PO

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

Study groups in NCT06802523
Study groupRoleWhat they receive
Schedule 1 (lintuzumab-Ac225, venetoclax, ASTX-727)ExperimentalINDUCTION: Patients receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR,PR or NR after cycle 1 receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
Receives: Radiation: Actinium Ac 225 Lintuzumab; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Decitabine and Cedazuridine; Drug: Venetoclax
Schedule 2 (lintuzumab-Ac225, venetoclax, ASTX-727)ExperimentalINDUCTION: Patients receive lintuzumab-Ac225 V over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR, PR or NR receive lintuzumab-Ac225 IV over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
Receives: Radiation: Actinium Ac 225 Lintuzumab; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Decitabine and Cedazuridine; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities

    Adverse events (AEs) will be described and graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

    Measured: Up to 28 days after the start of induction (up to 42 days for persistent neutropenia and thrombocytopenia)

  2. Overall response rate (ORR)

    Will include patients with complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete hematologic recovery (CRi). ORR and its 95% confidence interval will be calculated.

    Measured: Up to 5 years

Secondary outcomes (20)

  1. Maximum tolerated dose of lintuzumab Ac-225 when used in combination with venetoclax and ASTX-727

    Will be determined based on the totality of safety (specifically cytopenia), tolerability, clinical activity, as appropriate.

    Measured: Up to completion of dose-escalation phase (Part A)

  2. Frequency and severity of AEs

    Will be assessed using CTCAE v 5.0. Toxicity by severity will be summarized using descriptive statistics. Will be listed for each dose level and the tabulations of AEs will also be produced by severity and by relationship to the study drug.

    Measured: Up to 30 days after last dose of study treatment

  3. CR rate

    Will be evaluated per European Leukemia Network (ELN) 2022 response criteria. Will be defined as bone marrow blasts < 5%, absence of circulating blasts, absence of extramedullary disease, absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (1,000uL), and platelet count ≥ 100 x 10^9/L (100 000/uL).

    Measured: Up to 5 years

  4. Time to CR

    Will be evaluated per ELN 2022 response criteria.

    Measured: Up to 5 years

  5. CRh rate

    Will be evaluated per ELN 2022 response criteria. Will be defined as ANC ≥ 0.5 x 10^9/L (500/uL) and platelet count ≥ 50 x 10^9/L (50 000/uL), otherwise all other CR criteria met.

    Measured: Up to 5 years

  6. Time to CRh

    Will be evaluated per ELN 2022 response criteria.

    Measured: Up to 5 years

  7. CRi rate

    Will be evaluated per ELN 2022 response criteria. All CR criteria except for residual neutropenia < 1.0 x 10^9/L (1,000/uL) or thrombocytopenia < 100 x 10^9/L (100 000/uL).

    Measured: Up to 5 years

  8. Time to CRi

    All CR criteria except for residual neutropenia < 1.0 × 109/L (1,000/µL) or thrombocytopenia < 100 × 109/L (100 000/µL)

    Measured: Up to 5 years

  9. CR rate without minimal residual disease (MRD)

    Will be defined as CR with one or fewer residual leukemic blasts per 1,000 leukocytes as detected by multi-parameter flow cytometry (MFC). CR rate without MRD and its 95% confidence interval will be calculated.

    Measured: At end of induction and end of first and third consolidation cycles (cycle length = 28 days), assessed up to 5 years

  10. CRh rate without MRD

    Will be defined as CRh with one or fewer residual leukemic blasts per 1,000 leukocytes as detected by MFC. CRh rate without MRD and its 95% confidence interval will be calculated.

    Measured: At end of induction and end of first and third consolidation cycles (cycle length = 28 days), assessed up to 5 years

  11. CRi rate without MRD

    Will be defined as CRi with one or fewer residual leukemic blasts per 1,000 leukocytes as detected by MFC. CRi rate without MRD and its 95% confidence interval will be calculated.

    Measured: At end of induction and end of first and third consolidation cycles (cycle length = 28 days), assessed up to 5 years

  12. Time to achieve CR without MRD

    Evaluated using MFC. CR without MRD and its 95% confidence interval will be calculated.

    Measured: Up to 5 years

  13. Time to achieve CRh without MRD

    Evaluated using MFC. CRh without MRD and its 95% confidence interval will be calculated.

    Measured: Up to 5 years

  14. Time to achieve CRi without MRD

    Evaluated using MFC. CRi without MRD and its 95% confidence interval will be calculated.

    Measured: Up to 5 years

  15. Duration of remission

    Will be described using Kaplan-Meier product limit methods.

    Measured: From day of achieving CR, CRh, CRi to the date of hematological relapse or death from any cause, assessed up to 5 years

  16. Progression free survival

    Will be described using Kaplan-Meier product limit methods.

    Measured: Up to 5 years

  17. Event-free survival

    Will be described using Kaplan-Meier product limit methods.

    Measured: From day 1 of registration to the date of treatment failure, hematologic relapse from CR/CRh/CRi or death from any cause, whichever occurs first, assessed up to 5 years

  18. Overall survival

    Will be described using Kaplan-Meier product limit methods.

    Measured: From day 1 of registration to the date of death from any cause, assesesd up to 5 years

  19. Clinical activity between two lintuzumab-Ac225 administration schedules

    Clinical activity will be defined as a patient achieving CR/CRi/CRh/morphologic leukemia-free state or partial response.

    Measured: Up to 5 years

  20. Toxicity between two lintuzumab-Ac225 administration schedules

    Will be assessed on the frequency or severity of AEs.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2025
  2. Study start18 Nov 2026 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Why it stopped: Drug Supply Issues

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06802523
Sponsor's protocol ID
NCI-2025-00575
Other IDs
NCI-2025-00575, 10653, 10653, UM1CA186689
Status last verified
Aug 2026
First submitted
29 Jan 2025
Last updated
24 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Actinium Ac 225 Lintuzumab, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 1 site 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 27 inclusion and 18 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 24 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 1 site 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 toxicities (time frame: Up to 28 days after the start of induction (up to 42 days for persistent neutropenia and thrombocytopenia)). 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?

On the ClinicalTrials.gov record for NCT06802523.

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 24 Aug 2026.

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