This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Tagraxofusp is a recombinant protein consisting of IL-3 conjugated to a truncated diptheria toxin. The IL-3 attaches to the cancer cells and the toxic substance kills them. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Tagraxofusp and azacitidine may work better to kill cancer cells and eradicate measurable residual disease in patients with acute myeloid leukemia.
Tagraxofusp-Based Therapy to Eradicate Measurable Residual Disease of Acute Myelogenous Leukemia Prior to Allogeneic Hematopoietic Cell Transplantation
- To determine the safety and tolerability of tagraxofusp-erzs (tagraxofusp) with or without azacitidine in participants with acute myeloid leukemia (AML) in remission who are planned to undergo allogeneic hematopoietic cell transplantation (alloHCT).
- To estimate the rate of conversion from measurable residual disease (MRD) positive (>= 0.01% by multiparametric flow cytometry [MPFC]) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) after 1 or 2 cycles of investigational therapy.
II. To estimate the rate of conversion from MRD positive (>= 0.01% by MPFC) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) post-investigational therapy within 30 days prior to initiation of transplant conditioning regimen and at day +100 following alloHCT.
III. To evaluate if adverse effects of this investigational combination leads to delays in alloHCT.
IV. To evaluate if this investigational therapy results in liver toxicities after alloHCT such as sinusoidal obstruction syndrome.
- To evaluate relapse rate following alloHCT in participants who receive investigational therapy.
VI. To evaluate MRD progression following alloHCT in participants who receive investigational therapy.
VII. To evaluate 1-year survival following alloHCT in participants who receive investigational therapy.
- To estimate the rate of conversion from MRD positive to MRD negative by means of next generation sequencing.
II. To describe the level of CD123 expression on leukemia blasts in the bone marrow specimen at diagnosis and/or time of relapse and the association with achievement of MRD negativity post-investigational therapy.
III. To evaluate the number of days to full donor T-cell chimerism following alloHCT.
OUTLINE: This is a dose-escalation study of tagraxofusp-erzs . Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive tagraxofusp-erzs intravenously (IV) once daily (QD) over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive azacitidine subcutaneously (SC) daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 months.