Refractory Myelodysplastic SyndromePhase 1NCT06888323
Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment
A Phase 1 study testing Actinium Ac 225 Lintuzumab, Bone Marrow Aspiration and Buccal Swab in people with Refractory Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial tests the safety, side effects and best dose of lintuzumab-Ac225 for the treatment of patients with high risk myelodysplastic syndrome that has not responded to previous treatment (refractory). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called Ac225. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Myelodysplastic Syndrome
- What is being tested?
- Actinium Ac 225 Lintuzumab, Bone Marrow Aspiration and Buccal Swab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2026to 31 Dec 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 histologically or cytologically confirmed diagnosis of MDS by bone marrow biopsy by World Health Organization (2016) guidelines
- Patients with MDS who have progressed or had no response after 6 cycles of azacitidine or 4 cycles of decitabine
- Patients with MDS must have ≥ 5% myeloblasts
- Patients with demonstration of CD33 positive myeloblasts more than 25% on flow cytometry
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of lintuzumab-Ac225 in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
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- Serum direct bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × institutional ULN
- Creatinine clearance ≥ 60 mL/min (creatinine clearance [CrCl] will be calculated using actual body weight unless the patient is obese [body mass index (BMI) ≥ 30 kg/m²], in which case adjusted body weight will be used)
- 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 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
- The effects of lintuzumab-Ac225 on the developing human fetus are unknown. For this reason and because CD33 radiotherapy agents are known to be teratogenic, female patients of childbearing age must have had a negative serum pregnancy test within 14 days of initiation of dosing and must agree to use of two acceptable methods of birth control while on the study drug. A woman must agree to remain on a highly effective method throughout the study and for at least 6 months after the last dose of study drug. 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. During the study and for 3 months after receiving the last dose of study drug, men participating in this trial must use highly effective contraception. Men who are sexually active with a woman of childbearing potential must use a barrier method of contraception, such as a condom, in addition to ensuring use of a highly effective method of contraception. Men who are sexually active with a woman who is pregnant must use a condom. Male participants must also agree not to father a child or donate sperm during the study and for 3 months after receiving the 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 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 have active clinically significant graft vs. host disease (GVHD) or are on systemic corticosteroids
- Patients have clinically active central nervous system (CNS) leukemia
- Patients who are receiving any other investigational agents, such as experimental treatment in a clinical trial within the last 14 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research (e.g. medical device) not scientifically or medically compatible with this study
- Patients who are receiving any therapy that can result in increased toxicity on this study or confound the study findings, within the last 14 days or 5 half-lives, whichever is longer, prior to enrollment. Non-hematological adverse reactions to prior therapies, except alopecia and peripheral neuropathy, must have resolved to no more than grade 1
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lintuzumab-Ac225
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- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
- Pregnant women are excluded from this study because lintuzumab-Ac225 is a CD33 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
- The patient had major surgery within 14 days prior to enrollment
- No prior radiopharmaceutical therapy and no radiation therapy within the last 120 days prior to cycle 1 day 1 (C1D1), as this may contribute to added toxicity
- 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
Dana-Farber - Harvard Cancer Center LAO
Boston, Massachusetts, 02115
About this study
Official title: Phase 1 Study of Lintuzumab-Ac225 Monotherapy for Patients With Hypomethylating Agent-Refractory Myelodysplastic Syndrome
This phase I trial tests the safety, side effects and best dose of lintuzumab-Ac225 for the treatment of patients with high risk myelodysplastic syndrome that has not responded to previous treatment (refractory). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called Ac225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers Ac225 to kill them. Giving lintuzumab-Ac225 may be safe, tolerable and/or effective in treating patients with high risk, refractory myelodysplastic syndrome.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety, tolerability, and maximum tolerated dose of actinium ac 225 lintuzumab (lintuzumab-Ac225) monotherapy in myelodysplastic syndrome/neoplasm (MDS) patients whose disease is refractory to or progressing on hypomethylating agent (HMA) therapy.
SECONDARY OBJECTIVES:
- To observe and record anti-tumor activity. II. To determine the efficacy, complete remission rates/overall response rates (ORR) as per International Working Group (IWG) 2023 criteria, overall response rates (ORR), progression free survival (PFS), and overall survival (OS) of lintuzumab-Ac225 in MDS patients whose disease is refractory to or progressing on HMA therapy.
III. To perform bulk ribonucleic acid (RNA) sequencing to assess transcriptomic changes in MDS patients after HMA therapy.
IV. Dosimetry studies V. To study the correlation of absorbed radiation doses (in Gy) with adverse events and disease control.
OUTLINE: This is a dose-escalation study of lintuzumab-Ac225.
Patients receive lintuzumab-Ac225 intravenously (IV), over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo single photon emission computed tomography (SPECT)/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial.
After completion of study treatment, patients are followed for 90 days and then up to 5 years, to monitor therapy related diseases.
- Conditions
- Refractory Myelodysplastic Syndrome
- Being tested
- Actinium Ac 225 Lintuzumab, Bone Marrow Aspiration, Buccal Swab, Computed Tomography, Single Photon Emission Computed Tomography
- Medical subject headings
- Myelodysplastic Syndromes
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
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
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo SPECT/CT
Single Photon Emission Computed TomographyProcedure or surgery
Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography
Undergo SPECT/CT
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lintuzumab-Ac225) | Experimental | Patients receive lintuzumab-Ac225 IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo SPECT/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial. Receives: Radiation: Actinium Ac 225 Lintuzumab; Procedure: Bone Marrow Aspiration; Procedure: Buccal Swab; Procedure: Computed Tomography; Procedure: Single Photon Emission Computed Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Measured: Up to 70 days from first dose of lintuzumab-ac225
Secondary outcomes (6)
Complete remission rate
Calculated as per the 2023 myelodysplastic syndrome (MDS) response criteria.
Measured: Up to 90 days after completion of treatment
Overall response rate
Calculated as per the 2023 MDS response criteria.
Measured: Up to 90 days after completion of treatment
Progression free survival
Calculated as per the 2023 MDS response criteria.
Measured: Up to 90 days after completion of treatment
Overall survival
Calculated as per the 2023 MDS response criteria.
Measured: Up to 90 days after completion of treatment
Transcriptomic changes
Ribonucleic acid sequencing analysis will be performed from cryopreserved bone marrow samples.
Measured: At baseline and after cycle 2 (cycle lenth = 28 days)
Incidence of adverse events
Will be graded using Common Terminology Criteria for Adverse Events 5.0 and described by frequency, duration, and severity of treatment-emergent, treatment-related, and serious adverse events. All reported toxicities, regardless of attribution, will be summarized by toxicity type and maximum grade, and sorted by number of patients experiencing the toxicity for each dosing cohort and overall.
Measured: Up to 90 days after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2025
- Study start3 Sep 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Why it stopped: Drug Supply Issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Myelodysplastic SyndromeStudies 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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Talha Badar, Principal investigator, Dana-Farber - Harvard Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06888323
- Sponsor's protocol ID
- NCI-2025-01929
- Other IDs
- NCI-2025-01929, 10695, 10695, UM1CA186709
- Status last verified
- Sep 2026
- First submitted
- 20 Mar 2025
- Last updated
- 9 Sep 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 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Lintuzumab-Ac225 Monotherapy for Patients With Hypomethylating Agent-Refractory Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT06888323
- Acronym / sponsor ID
- NCI-2025-01929
- Conditions
- Refractory Myelodysplastic Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Drug Supply Issues
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 3 Sep 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 21 Mar 2025 (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 the safety, side effects and best dose of lintuzumab-Ac225 for the treatment of patients with high risk myelodysplastic syndrome that has not responded to previous treatment (refractory). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called Ac225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers Ac225 to kill them. Giving lintuzumab-Ac225 may be safe, tolerable and/or effective in treating patients with high risk, refractory myelodysplastic syndrome.
Detailed description
PRIMARY OBJECTIVE:
- To determine the safety, tolerability, and maximum tolerated dose of actinium ac 225 lintuzumab (lintuzumab-Ac225) monotherapy in myelodysplastic syndrome/neoplasm (MDS) patients whose disease is refractory to or progressing on hypomethylating agent (HMA) therapy.
SECONDARY OBJECTIVES:
- To observe and record anti-tumor activity. II. To determine the efficacy, complete remission rates/overall response rates (ORR) as per International Working Group (IWG) 2023 criteria, overall response rates (ORR), progression free survival (PFS), and overall survival (OS) of lintuzumab-Ac225 in MDS patients whose disease is refractory to or progressing on HMA therapy.
III. To perform bulk ribonucleic acid (RNA) sequencing to assess transcriptomic changes in MDS patients after HMA therapy.
IV. Dosimetry studies V. To study the correlation of absorbed radiation doses (in Gy) with adverse events and disease control.
OUTLINE: This is a dose-escalation study of lintuzumab-Ac225.
Patients receive lintuzumab-Ac225 intravenously (IV), over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo single photon emission computed tomography (SPECT)/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial.
After completion of study treatment, patients are followed for 90 days and then up to 5 years, to monitor therapy related diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lintuzumab-Ac225) | Experimental | Radiation: Actinium Ac 225 Lintuzumab, Procedure: Bone Marrow Aspiration, Procedure: Buccal Swab, Procedure: Computed Tomography, Procedure: Single Photon Emission Computed TomographyPatients receive lintuzumab-Ac225 IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo SPECT/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically or cytologically confirmed diagnosis of MDS by bone marrow biopsy by World Health Organization (2016) guidelines
- Patients with MDS who have progressed or had no response after 6 cycles of azacitidine or 4 cycles of decitabine
- Patients with MDS must have ≥ 5% myeloblasts
- Patients with demonstration of CD33 positive myeloblasts more than 25% on flow cytometry
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of lintuzumab-Ac225 in patients < 18 years of age, children are excluded from this study
Key exclusion criteria (11 listed)
- 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 have active clinically significant graft vs. host disease (GVHD) or are on systemic corticosteroids
- Patients have clinically active central nervous system (CNS) leukemia
- Patients who are receiving any other investigational agents, such as experimental treatment in a clinical trial within the last 14 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research (e.g. medical device) not scientifically or medically compatible with this study
- Patients who are receiving any therapy that can result in increased toxicity on this study or confound the study findings, within the last 14 days or 5 half-lives, whichever is longer, prior to enrollment. Non-hematological adverse reactions to prior therapies, except alopecia and peripheral neuropathy, must have resolved to no more than grade 1
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 |
|---|---|---|
| Actinium Ac 225 LintuzumabAlso: 225Ac-HuM195, Actimab-A, Actinium (225Ac) Lintuzumab Satetraxetan, Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195Given IV | Radiation | Treatment (lintuzumab-Ac225) |
| Bone Marrow AspirationUndergo bone marrow aspiration | Procedure or surgery | Treatment (lintuzumab-Ac225) |
| Buccal SwabAlso: Buccal Scraping, Buccal Smear, Buccal swab/scraping, Buccal SwabbingUndergo buccal swab | Procedure or surgery | Treatment (lintuzumab-Ac225) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo SPECT/CT | Procedure or surgery | Treatment (lintuzumab-Ac225) |
| Single Photon Emission Computed TomographyAlso: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomographyUndergo SPECT/CT | Procedure or surgery | Treatment (lintuzumab-Ac225) |
Primary outcome
Maximum tolerated dose
Time frame: Up to 70 days from first dose of lintuzumab-ac225
6 secondary outcomes
Complete remission rate
Time frame: Up to 90 days after completion of treatment
Overall response rate
Time frame: Up to 90 days after completion of treatment
Progression free survival
Time frame: Up to 90 days after completion of treatment
Overall survival
Time frame: Up to 90 days after completion of treatment
Transcriptomic changes
Time frame: At baseline and after cycle 2 (cycle lenth = 28 days)
Incidence of adverse events
Time frame: Up to 90 days after completion of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 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.
Talha Badar principal investigator
Dana-Farber - Harvard Cancer Center LAO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Actinium Ac 225 Lintuzumab, Bone Marrow Aspiration and Buccal Swab in people with Refractory Myelodysplastic Syndrome, 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 15 inclusion and 11 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 9 Sep 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?
Maximum tolerated dose (time frame: Up to 70 days from first dose of lintuzumab-ac225). 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 9 Sep 2026.