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The aggregation of attractive colloids has been extensively studied from both theoretical and experimental perspectives as the fraction of solid particles is changed, and the range, type, and strength of attractive or repulsive forces between particles varies. The resulting gels, consisting of disordered assemblies of attractive colloidal particles, have also been investigated with regards to percolation, phase separation, and the mechanical characteristics of the resulting fractal networks. Despite tremendous progress in our understanding of the gelation process, and the exploration of different routes for arresting the dynamics of attractive colloids, the complex interplay between convective transport processes and many-body effects in such systems has limited our ability to drive the system toward a specific configuration. Here, we study a model attractive colloidal system over a wide range of particle characteristics and flow conditions undergoing aggregation far from equilibrium. The complex multiscale dynamics of the system can be understood using a time-rate-transformation diagram adapted from understanding of materials processing in block copolymers, supercooled liquids, and much stiffer glassy metals to direct targeted assembly of attractive colloidal particles. Keywords: Colloidal gels, Directed assembly, Rheology, Attractive colloids, Targeted-design of colloids

Purpose: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models., Patients and Methods: Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML., Results: Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD-positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD-negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD-indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay., Conclusion: Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.