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Acute Myeloid LeukemiaPhase 1NCT06498973

Tagraxofusp and Azacitidine for Maintenance Treatment in Patients With CD123 Positive AML and MDS Following Donor Hematopoietic Cell Transplant

A Phase 1 study testing Azacitidine, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase Ib trial tests the safety, side effects, best dose and effectiveness of tagraxofusp in combination with azacitidine as maintenance therapy in treating patients with CD123 positive acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after a donor (allogeneic) hematopoietic cell transplant. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Azacitidine, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
28 Jan 2025to 25 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Age: 18-75 years old
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • First or second allogeneic HCT-eligible patients with AML or MDS with high-risk cytogenetics per European LeukemiaNet (ELN) (AML) or Revised International Prognostic Scoring System (R-IPSS) (MDS); or by having active (morphological) or minimal residual disease (MRD)+ status at the time of HCT (by multicolor flowcytometry, cytogenetics or molecular testing) OR patients who underwent HCT for AML or MDS with high-risk cytogenetics per ELN (AML) or R-IPSS (MDS)
Show all 41Show fewer
  • Positive for CD123 by flow cytometry of either peripheral blood or bone marrow aspirates at the time of diagnosis at any time-point prior to HCT. (Note: CD123 measurement will be conducted using the 10-color Beckman Coulter Navios XL flow cytometer. We will use CD123 PE [Beckman Coulter #A32535] to gate the abnormal population of interest. This population will be compared to the internal negative control population [e.g., T-cells]. If more than 20% of the abnormal population is positive relative to this control, it will be classified as positive.)
  • Any conditioning regiment or GVHD prophylaxis is allowed
  • Any donor (i.e., match related/unrelated, mismatched, haploidentical, etc.) or graft source (i.e., bone marrow, mobilized peripheral blood stem cells, etc.) is allowed
  • Prior treatment with CD123-therapy is allowed if no progression is documented on therapy
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • STUDY MAINTENANCE TREATMENT: Complete response (CR) or MRD-positive on day 30 bone marrow biopsy (BMB) for disease assessment
  • STUDY MAINTENANCE TREATMENT: Patients must be fully engrafted after HCT before starting the first cycle of maintenance. Full engraftment is defined as absolute neutrophil count (ANC) of 500 or above for 3 days and platelet count of more than 20,000 without transfusion for 7 consecutive days
  • STUDY MAINTENANCE TREATMENT: ECOG ≤ 2
  • STUDY MAINTENANCE TREATMENT: No treatment with anti-CD123 therapy after allogeneic HCT
  • STUDY MAINTENANCE TREATMENT: No evidence of active or uncontrolled infection
  • STUDY MAINTENANCE TREATMENT: No active GVHD; prednisone dose of ≤ 10 mg/daily is allowed
  • STUDY MAINTENANCE TREATMENT: ANC ≥ 1.5 (within 7 days of day 1 of the cycle 1)
  • NOTE: Transfusion (red blood cells [RBC] or platelet) to achieve the above-mentioned counts is allowed
  • STUDY MAINTENANCE TREATMENT: Hemoglobin (HbG) ≥ 7 (within 7 days of day 1 of the cycle 1)
  • NOTE: Transfusion (RBC or platelet) to achieve the above-mentioned counts is allowed
  • STUDY MAINTENANCE TREATMENT: Platelet count ≥ 20K (within 7 days of day 1 of the cycle 1)
  • NOTE: Transfusion (RBC or platelet) to achieve the above-mentioned counts is allowed
  • STUDY MAINTENANCE TREATMENT: Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 7 days of day 1 of the cycle 1)
  • STUDY MAINTENANCE TREATMENT: Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 7 days of day 1 of the cycle 1)
  • STUDY MAINTENANCE TREATMENT: Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 7 days of day 1 of the cycle 1)
  • STUDY MAINTENANCE TREATMENT: Serum albumin > 3.2 (within 7 days of day 1 of the cycle 1) (note that albumin infusions are not permitted in order to enable eligibility but can be given after treatment starts)
  • STUDY MAINTENANCE TREATMENT: Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 7 days of day 1 of the cycle 1)
  • STUDY MAINTENANCE TREATMENT: If not receiving anticoagulants: International normalized ratio (INR) or prothrombin (PT) ≤ 1.5 x ULN (within 7 days of day 1 of the cycle 1)
  • If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • STUDY MAINTENANCE TREATMENT: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 7 days of day 1 of the cycle 1)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • STUDY MAINTENANCE TREATMENT: The Patient should agree to use acceptable contraceptive methods for the duration of the time in the study, and to continue to use contraceptive methods for 6 months following the end of study therapy
  • STUDY MAINTENANCE TREATMENT: The patient may not have persistent clinically significant toxicities grade ≥ 1 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
  • STUDY MAINTENANCE TREATMENT: The patient has not received treatment with another investigational agent within 14 days of study entry
  • STUDY MAINTENANCE TREATMENT: The patient does not have clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
  • STUDY MAINTENANCE TREATMENT: The patient does not have uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study
  • STUDY MAINTENANCE TREATMENT: The patient does not have known active or suspected central nervous system (CNS) disease. If suspected, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid
  • STUDY MAINTENANCE TREATMENT: The patient does not have uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
  • STUDY MAINTENANCE TREATMENT: The patient does not have any condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities

Who cannot join

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents (tagraxofusp and azacitidine)
  • Females only: Pregnant or breastfeeding
  • Any other condition including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness, that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • The patient has an active malignancy and/or cancer history that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease
  • The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
  • The patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study
Show all 10Show fewer
  • The patient has known active or suspected central nervous system (CNS) disease. If suspected, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid
  • Active hepatitis B or C or HIV infection
  • The patient has any condition which, in the opinion of the investigator, places the patient at an unacceptably high risk for toxicities
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Monzr M. Al Malki, MD contact

626-407-1957

malmalki@coh.org

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Hoda Z. Pourhassan, 626-218-2405, hpourhassan@coh.org

    Hoda Z. Pourhassan, MD

    Recruiting

Other trials in United States

About this study

Official title: CD123 Antibody Toxin Congregate (CD123 ATC; Tagraxofusp) Combined With Azacitidine for Maintenance Therapy Post Allogeneic Hematopoietic Cell Transplantation for Patients With CD123-Positive Malignant

This phase Ib trial tests the safety, side effects, best dose and effectiveness of tagraxofusp in combination with azacitidine as maintenance therapy in treating patients with CD123 positive acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after a donor (allogeneic) hematopoietic cell transplant. An allogeneic hematopoietic cell transplant (HCT) is a type of transplant where the cancer patient receives cells from another person. Maintenance therapy is given after the transplant to prevent the cancer from coming back. Tagraxofusp is a drug that targets cells that have CD123 on their surface in order to kill the cancer cells to help prevent the cancer from coming back. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Giving tagraxofusp in combination with azacitidine may be safe, tolerable and/or effective maintenance therapy in patients with CD123 positive AML and MDS after an allogeneic HCT.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Evaluate the safety and feasibility of tagraxofusp-erzs (tagraxofusp) with a fixed dose of azacitidine and determine the recommended phase 2 dose (RP2D) for tagraxofusp in patients with CD123-positive hematological malignancy when given as maintenance therapy following allogeneic transplant (HCT).

SECONDARY OBJECTIVES:

  1. Estimate overall survival (OS), progression-free survival (PFS) and the cumulative incidence of relapse and non-relapse mortality (NRM) at 100 days and 1 year after starting maintenance therapy.

II. Evaluate the cumulative incidence of grade 2-4 and 3-4 acute graft-versus-host disease (GVHD) at 100 days post-HCT, secondary graft failure, and chronic GVHD at 1-year after HCT.

III. Estimate the cumulative incidence of infections in the first 100 days from the start of maintenance therapy.

EXPLORATORY OBJECTIVES:

  1. Describe kinetics of immune cell recovery during 1st year post-HCT and during maintenance therapy with tagraxofusp-azacitidine (TAG-AZA).

II. Assess the possible correlation between chimerism kinetics (per next generation sequencing [NGS]/ quantitative polymerase chain reaction [qPCR] assay) and post-HCT relapse during maintenance therapy with TAG-AZA.

III. Characterize the presence and level of GVHD biomarkers and inflammatory cytokines in the first 100 days from the start of maintenance therapy.

IV. Assess patients' quality of life (QOL) at baseline (before initiation of the first cycle) then at the end of cycles 3 and 6 (± 2 weeks); optional questionnaire.

  1. Longitudinally assess CD123 expression on hematopoietic cells. VI. Assess changes in symptoms of chronic GVHD using Lee Symptom Scale; patient self-report.

VII. Describe transplant outcomes defined in the secondary objectives among all consented patients regardless of receiving the study therapy.

OUTLINE: This is a dose-escalation study of tagraxofusp in combination with azacitidine followed by a dose-expansion study.

Patients receive tagraxofusp intravenously (IV) over 15 minutes once daily (QD) on days 1-3 and azacitidine IV over 10-40 minutes QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone marrow aspiration and biopsy on study.

After completion of study treatment, patients are followed up at 30 days and then annually for up to 2 years after start of protocol therapy.

Being tested
Azacitidine, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Questionnaire Administration
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, 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

  • Questionnaire AdministrationOther

    Ancillary studies

  • Tagraxofusp-erzsBiological

    Also called Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris

    Given IV

Study groups in NCT06498973
Study groupRoleWhat they receive
Treatment (tagraxofusp, azacitidine)ExperimentalPatients receive tagraxofusp IV over 15 minutes QD on days 1-3 and azacitidine IV over 10-40 minutes QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone marrow aspiration and biopsy on study.
Receives: Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Other: Questionnaire Administration; Biological: Tagraxofusp-erzs

What is being measured

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

  1. Incidence of adverse events (AEs)

    Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. AEs will be recorded by type, severity, duration, and attribution or association with the study regimen and occurrence. Tables will be constructed to summarize the observed incidence, severity and type of toxicity. Point estimates and corresponding exact 95% confidence intervals (CIs) will be provided for each measure of toxicity/AEs.

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

  2. Dose limiting toxicities (DLT)

    DLTs will be graded according to the NCI CTCAE v5.0. AEs will be recorded by type, severity, duration, and attribution or association with the study regimen and occurrence. Tables will be constructed to summarize the observed incidence, severity and type of toxicity. Point estimates and corresponding exact 95% CIs will be provided for each measure of toxicity/AEs.

    Measured: Up to the end of cycle 1 on day 28

  3. Percent of patients completing at least 3 cycles at assigned dose level

    Feasibility will be defined as 50% of patients completing at least 3 cycles of maintenance therapy at the assigned dose level. The point estimate and exact 95% CIs will be provided.

    Measured: Up to 180 days

Secondary outcomes (8)

  1. Overall survival (OS)

    OS will be analyzed using the Kaplan-Meier curves.

    Measured: From start of protocol therapy to death, assessed at 100 days and 1 year

  2. Progression-free survival (PFS)

    PFS will be analyzed using the Kaplan-Meier curves.

    Measured: From start of protocol therapy to relapse or progression, or death, assessed at 100 days and 1 year

  3. Relapse/progression

    Measured: From start of therapy to the first observation of relapse or progression, assessed at 100 days and 1 year

  4. Non-relapse mortality

    Measured: From start of therapy until non-disease related death, assessed at 100 days and 1 year

  5. Incidence of grades 2-4 and 3-4 acute graft versus host disease (aGVHD)

    AGVHD will be estimated using the cumulative incidence curve. AGVHD will be graded according to the Mount Sinai Acute Graft Versus Host Disease International Consortium Grading System.

    Measured: From start of protocol therapy to aGVHD onset date, assessed up to 100 days

  6. Incidence of secondary graft failure

    Incidence of secondary graft failure will be defined as cytopenias after initial engraftment (absolute neutrophil count < 500/uL) with donor chimerism of less than 5% or falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion or death due to cytopenias, and fall in donor chimerism, even if chimerism was > 5%.

    Measured: Up to 1 year post transplant

  7. Incidence of chronic graft versus host disease (cGVHD)

    CGVHD will be scored according to National Institute of Health Consensus Staging. CGVHD will be estimated using the cumulative incidence curve.

    Measured: From start of protocol therapy to cGVHD onset date, assessed up to 1 year post transplant

  8. Infection rate

    Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: In the first 100 days from the start of maintenance therapy

Timeline

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

  1. First posted12 Jul 2024
  2. Study start28 Jan 2025
  3. Primary completion25 Apr 2027 (estimated)
  4. Study completion25 Apr 2027 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06498973
Sponsor's protocol ID
23400
Other IDs
NCI-2024-05359, 23400, P30CA033572
Status last verified
Jul 2026
First submitted
5 Jul 2024
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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 and Myelodysplastic Syndrome, run by City of Hope Medical Center 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 41 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 16 Jul 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Monzr M. Al Malki, MD (626-407-1957, malmalki@coh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) (time frame: Up to 30 days after last dose of study treatment). The study lists 3 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 NCT06498973.

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 16 Jul 2026.

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