NCT06498973

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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: I. 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. V. 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.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
OTHER	Questionnaire Administration	Ancillary studies
BIOLOGICAL	Tagraxofusp-erzs	Given IV

Timeline

• Start date: 2025-01-28
• Primary completion: 2027-04-25
• Completion: 2027-04-25
• First posted: 2024-07-12
• Last updated: 2026-03-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study