The investigators hypothesize that flotetuzumab for relapsed AML following allo-HCT will be safe, tolerable and may facilitate preferential immune effector cell retargeting of leukemic cells resulting in improved patient outcomes. Furthermore, administration of a donor lymphocyte infusion (DLI) (if available) in combination with flotetuzumab will be safe, tolerable and may provide additional therapeutic efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Will be provided by MacroGenics Inc.
DLI represents a non-specific form of adoptive cell therapy which involves infusion of a pool of allogeneic immune cells, including CD4+ T cells, CD8+ T cells, regulatory T cells (T Regs), natural killer (NK) cells and professional antigen presenting cells.
Washington University School of Medicine
St Louis, Missouri, United States
Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi
* Complete remission without minimal residual disease (CRmrd): CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Efficacy as Measured by Number of Participants With CR and CRi
* Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Overall Response Rate
* Defined as partial remission or better * PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Morphologic Leukemia-free State (MLFS) Rate
\- MLFS: Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Partial Remission (PR) Rate
\- PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Stable Disease (SD) Rate
\- SD: Absence of CR(mrd), CR, CRi, PR, MLFS; and criteria for PD not met
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Progression-free Survival (PFS) Rate
* PFS will be calculated as the time from the start of the first dose of study drug until the occurrence of disease progression or death from any cause, respectively * Progressive disease: Evidence for an increase in bone marrow blast percentage (\>50% over baseline), and/or increase of absolute blast counts in the blood (\>50% to \>25 × 10\^9/L) without differentiation syndrome, or new extramedullary disease
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Overall Survival (OS)
-OS will be calculated as the time from the start of the first dose of study drug until the occurrence of death from any cause.
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Number of Participants With Adverse Events as Measured by CTCAE v5.0
Time frame: From start of treatment through 28 days following completion of treatment (median length of 59 days, full range 11-99 days).
Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines
* Grade 1:Symptoms are not life threatening and require symptomatic treatment only, e.g., fever, nausea, fatigue, headache, myalgias, malaise * Grade 2: Symptoms require and respond to moderate intervention; oxygen requirement \< 40% or hypotension responsive to fluids or low-dose of one vasopressor or grade 2 organ toxicity * Grade 3: Symptoms require and respond to aggressive intervention; oxygen requirement ≥ 40% or hypotension requiring high-dose vasopressors or multiple vasopressors or grade 3 organ toxicity (except transaminitis) or grade 4 transaminitis * Grade 4: Life-threatening symptoms; requirement for ventilator support or grade 4 organ toxicity (excluding transaminitis) * Grade 5 Death
Time frame: Through the end of Cycle 2 (each cycle is 28 days)
Number of Participants With Neurotoxicity as Measured by 2019 ASTCT Consensus Guidelines
Time frame: Through the end of Cycle 2 (each cycle is 28 days)
Number of Participants With Acute Graft Versus Host Disease (GvHD) as Measured by MAGIC Criteria
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Number of Participants With Chronic Graft Versus Host Disease (GvHD) as Measured by NIH Severity Score
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
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