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.
PRIMARY OBJECTIVE: I. 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). SECONDARY OBJECTIVES: I. 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. V. 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. EXPLORATORY OBJECTIVES: I. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Given SC
Given IV
Habtemariam,Bruck
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Dose-limiting toxicity
Grade \>= 3 toxicity using Common Terminology Criteria for Adverse Events version 5.0 or severe persistent hematologic toxicity defined as absolute neutrophil count (ANC) \< 500/uL OR platelet count \< 10,000/uL in participants that have morphologic leukemia-free state (bone marrow blasts \< 5%) are conditions for a dose limiting toxicity.
Time frame: Up to 42 days
Measurable residual disease (MRD)
As measured by the University of Washington multiparametric flow cytometry (MPFC) assay with sensitivity of 0.01%
Time frame: At the end of cycle 1 and cycle 2 (each cycle is 28 days).
MRD
As measured by the University of Washington MPFC assay with sensitivity of 0.01%.
Time frame: Within 30 days prior to initiation of transplant conditioning regimen and at day 100 after transplant
Number of days between investigational regimen day 28 and initiation of transplant conditioning regimen
Time frame: Between investigational regimen day 28 and initiation of transplant conditioning regimen, through study completion, an average of 1 year.
Rate of sinusoidal obstruction syndrome
Time frame: up to 1 year following investigational therapy
Relapse
As defined by International Working Group criteria: the relapse rate and median duration of remission following allogeneic hematopoietic cell transplantation (HCT) will be reported along with an exact 95% confidence interval.
Time frame: Up to 1 year
MRD progression
Defined by presence of leukemia blasts \>0.01% at any time after achieving MRD negativity (\<0.01%).
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Time frame: Up to 1 year
Overall survival
Kaplan-Meier methods will estimate the overall survival at 1 year following allogeneic (allo)HCT. This analysis will be performed using the FAS. The 1-year survival estimate will be reported along with a 95% confidence interval.
Time frame: 1 year after transplant