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Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1

Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML

A Phase Ia/Ib Study of Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML

NCT05716009•Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

View on ClinicalTrials.gov

Summary

This is an open-label Phase Ia/Ib clinical study of tagraxofusp-erzs, a novel cytokine-drug conjugate that links interleukin-3 with a truncated diphtheria toxin, in combination with gemtuzumab ozogamicin for patients with relapsed/refractory AML. The primary objective of the study is to determine the recommended phase 2 dose (RP2D) of tagraxofusp-erzs in combination with gemtuzumab ozogamicin in this patient population. Then, once RP2D is determined, to determine the safety and tolerability of combination gemtuzumab and tagraxofusp-erzs when administered at the RP2D.

Detailed Description

The goal of this study is to study the safety and tolerability of a novel combination of medications in relapsed or refractory AML: tagraxofusp and gemtuzumab ozogamicin. If the combination is found to be safe, then further studies will be done to determine whether this combination is effective for AML. The first part of this study is called phase 1A. This part of the study is done to determine the optimal dose of tagraxofusp that can be given with gemtuzumab. The main purpose of phase 1A is to test different doses of the study drug, starting with the lowest dose and determining the optimal dose. In phase 1B (the second part of the study), this dose will be given along with gemtuzumab to a larger group of patients to further test the safety and tolerability of this combination. The results of phase IB will also be used to determine whether the combination of tagraxofusp, when given at the optimal dose, and gemtuzumab are effective in treating AML. Substances (biomarkers) found in the blood and bone marrow will be drawn from patients in the course of this study to better understand whether the combination is effective against AML.

Eligibility

Age

12 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•• Histologically confirmed diagnosis of acute myeloid leukemia (AML) according per 2016 World Health Organization (WHO) criteria.
•* Cluster of differentiation marker (CD)33 and CD123 / interleukin (IL)3RA expression on the subject's blasts, determined by standard Flow AML MRD assay.
•* Age ≥ 12
•* Relapsed or refractory after one cycle of prior therapy (cytoreductive agents such as hydroxyurea, cyclophosphamide, or a single dose of gemtuzumab ozogamicin are not considered prior treatment regimens).
•* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
•* Adequate baseline organ function, including cardiac, renal, and hepatic function as defined by:
•* Left ventricular ejection fraction (LVEF) ≥ 50% by multi-gated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to the start of therapy
•* No clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
•* Creatinine Clearance (CrCl) ≥ 60mL/min
•* Serum albumin ≥ 3.2 g/dL (note that albumin infusions are not permitted in order to enable eligibility)
+8 more criteria

Exclusion Criteria

•• Prior treatment with tagraxofusp-erzs.
•* Primary resistance to or progression on gemtuzumab. Patients who have previously received Gemtuzumab, but whose disease was not resistant or did not progress on it are eligible.
•* Active central nervous system involvement. Patients with a history of central nervous system involvement that has cleared with prior treatments are eligible.
•* Blood or bone marrow transplant within 60 days of screening or active graft versus host disease.
•* The patient has persistent clinically significant toxicities Grade ≥ 2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
•* The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
•* 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 is receiving immunosuppressive therapy - with the exception of low-dose prednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.
+4 more criteria

Locations (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Key Dates

Start Date

November 20, 2023

Primary Completion Date

December 25, 2027

Completion Date

December 25, 2028

Last Updated

May 6, 2025

Enrollment

ESTIMATED participants

Conditions

Acute Myeloid Leukemia

Interventions

Dose Escalation -tagraxofusp-erzs

DRUG

Dose Expansion at RP2D -tagraxofusp-erzs

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 6, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML

Inclusion Criteria

Exclusion Criteria

Phase I Study of HC-7366 for Acute Myeloid Leukemia

VAC Regimen for AML Patients Who Failed to Response to VA Regimen

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

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