Tagraxofusp and Azacitidine for Maintenance Treatment in Patients With CD123 Positive AML and MDS Following Donor Hematopoietic Cell Transplant
NCT Number: NCT06498973
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Acute Myeloid Leukemia|Myelodysplastic Syndrome
Interventions: DRUG: Azacitidine|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|OTHER: Questionnaire Administration|BIOLOGICAL: Tagraxofusp-erzs
Sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 43
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2025-01-20
Completion Date: 2027-01-20
Locations: City of Hope Medical Center, Duarte, California, 91010, United States

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.

Primary Outcome Measures: 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 Outcome Measures: Overall survival (OS), OS will be analyzed using the Kaplan-Meier curves., From start of protocol therapy to death, assessed at 100 days and 1 year|Progression-free survival (PFS), PFS will be analyzed using the Kaplan-Meier curves., 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), 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., From start of protocol therapy to aGVHD onset date, assessed up to 100 days|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%., Up to 1 year post transplant|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., From start of protocol therapy to cGVHD onset date, assessed up to 1 year post transplant|Infection rate, Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any., In the first 100 days from the start of maintenance therapy