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

NCT06498973 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23400NCI-2024-05359P30CA033572
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 30 days after last dose of study treatment

• 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.

  Up to the end of cycle 1 on day 28

• 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.

  Up to 180 days

Secondary Outcomes (8)

• Overall survival (OS)

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

• Progression-free survival (PFS)

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

• Relapse/progression

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

• Non-relapse mortality

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

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

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

Study Arms (1)

Treatment (tagraxofusp, azacitidine)

EXPERIMENTAL

Patients 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.

Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Other: Questionnaire Administration; Biological: Tagraxofusp-erzs

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (tagraxofusp, azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (tagraxofusp, azacitidine)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (tagraxofusp, azacitidine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (tagraxofusp, azacitidine)

Questionnaire Administration OTHER

Ancillary studies

Treatment (tagraxofusp, azacitidine)

Tagraxofusp-erzs BIOLOGICAL

Given IV

Also known as: Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL 401, SL-401, SL401, Tagraxofusp, Tagraxofusp ERZS

Treatment (tagraxofusp, azacitidine)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine; Specimen Handling; Biopsy; tagraxofusp

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Hoda Z Pourhassan, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hoda Pourhassan, MD

CONTACT

6262182405; hpourhassan@coh.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 12, 2024
• Study Start: January 28, 2025
• Primary Completion (Estimated): April 25, 2027
• Study Completion (Estimated): April 25, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)