Abstract: The present invention includes methods for treating a proliferative disorder comprising administering a therapeutically effective amount of crenolanib or a salt thereof in combination with pharmaceutical agent targeting apoptosis pathway proteins wherein the crenolanib and other agent are provided at least one of sequentially or concomitantly in a subject for use in the treatment of the proliferative disease, wherein the subject is a human subject.

Abstract: The present invention includes methods for treating a proliferative disorder in a subject with mutated or constitutively active FLT3 in a subject relapsed/refractory to one or more prior tyrosine kinase inhibitors comprising: obtaining a tumor sample from the subject that is relapsed/refractory to one or more prior tyrosine kinase inhibitors; measuring expression of mutated or constitutively active FLT3 mutant in the tumor sample; and administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof sufficient to treat the proliferative disorder.

Abstract: The present invention includes methods for treating a proliferative disorder in a subject with mutated or constitutively active FLT3 in a subject relapsed/refractory to one or more prior tyrosine kinase inhibitors comprising: obtaining a tumor sample from the subject that is relapsed/refractory to one or more prior tyrosine kinase inhibitors; measuring expression of mutated or constitutively active FLT3 mutant in the tumor sample; and administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof sufficient to treat the proliferative disorder.

Abstract: The present invention includes a method of inhibiting or reducing deregulated FLT3 tyrosine kinase activity or FLT3 tyrosine kinase expression in a subject with a proliferative disease by administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I: or pharmaceutically acceptable salt thereof.

Abstract: The present invention includes a method of inhibiting or reducing deregulated FLT3 tyrosine kinase activity or FLT3 tyrosine kinase expression in a subject with a proliferative disease by administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I: or pharmaceutically acceptable salt thereof.

Abstract: The present invention includes a method of reducing or inhibiting the kinase activity of C-KIT mutant tyrosine kinase activity in a cell or a subject, and the use of such compound for treating mutant C-KIT driven cell proliferative disorder(s) in a subject related to using a compound of the present invention: or pharmaceutically acceptable salt thereof, wherein the C-KIT mutation is located in at least one of exon 8, exon 9, exon 11, exon 13, exon 14, or exon 17.

Abstract: The present invention includes methods for treating a proliferative disorder by blocking both PDGFR and VEGFR signaling comprising a therapeutically effective amount of crenolanib or salt in combination with a VEGF/VEGFR inhibitor that is not axitinib wherein the crenolanib, VEGF/VEGFR inhibitor that is not axitinib are provided at least one of sequentially or concomitantly, in a subject for use in the treatment of the proliferative disorder, wherein the subject is a human subject.

Abstract: The present invention includes a method of reducing or inhibiting the kinase activity of C-KIT mutant tyrosine kinase activity in a cell or a subject, and the use of such compound for treating mutant C-KIT driven cell proliferative disorder(s) in a subject related to using a compound of the present invention: or pharmaceutically acceptable salt thereof, wherein the C-KIT mutation is located in at least one of exon 8, exon 9, exon 11, exon 13, exon 14, or exon 17.

Abstract: The present invention includes methods for treating a proliferative disorder in a subject with mutated or constitutively active FLT3 in a subject relapsed/refractory to one or more prior tyrosine kinase inhibitors comprising: obtaining a tumor sample from the subject that is relapsed/refractory to one or more prior tyrosine kinase inhibitors; measuring expression of mutated or constitutively active FLT3 mutant in the tumor sample; and administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof sufficient to treat the proliferative disorder.

Abstract: The present invention includes methods for treating a proliferative disorder by blocking both PDGFR and VEGFR signaling comprising a therapeutically effective amount of crenolanib or salt in combination with a VEGF/VEGFR inhibitor that is not axitinib wherein the crenolanib, VEGF/VEGFR inhibitor that is not axitinib are provided at least one of sequentially or concomitantly, in a subject for use in the treatment of the proliferative disorder, wherein the subject is a human subject.

Abstract: The present invention includes methods for treating TRKA, TRKB, and/or TRKC driven proliferative disorder in a subject comprising administering to the subject a therapeutically effective amount of crenolanib, wherein the subject has a proliferative disorder with overexpression, activation, amplification, or mutation of TRKA, TRKB, and/or TRKC kinase.

Abstract: The present invention includes methods of monitoring measurable residual disease in patients suffering from a proliferative disorder, determining which patients could benefit from treatment or intervention with crenolanib or salt in reducing residual disease and maintaining remission, and administering a therapeutically effective amount of crenolanib as a single agent or sequentially or concomitantly with another therapeutic agent.

Abstract: The present invention relates to the use of crenolanib, in a pharmaceutically acceptable salt form for the treatment of FLT3 mutated proliferative disorders driven by constitutively activated mutant FLT3, and to a method of treatment of warm-blooded animals, preferably humans, in which a therapeutically effective dose of crenolanib is administered to an animal suffering from said disease or condition:

Abstract: The present invention includes methods for treating TRKA, TRKB, and/or TRKC driven proliferative disorder in a subject comprising administering to the subject a therapeutically effective amount of crenolanib, wherein the subject has a proliferative disorder with overexpression, activation, amplification, or mutation of TRKA, TRKB, and/or TRKC kinase.

Abstract: The present invention includes methods of monitoring measurable residual disease in patients suffering from a proliferative disorder, determining which patients could benefit from treatment or intervention with crenolanib or salt in reducing residual disease and maintaining remission, and administering a therapeutically effective amount of crenolanib as a single agent or sequentially or concomitantly with another therapeutic agent.

Abstract: The present invention relates to the use of crenolanib, in a pharmaceutically acceptable salt form for the treatment of FLT3 mutated proliferative disorders driven by constitutively activated mutant FLT3, and to a method of treatment of warm-blooded animals, preferably humans, in which a therapeutically effective dose of crenolanib is administered to an animal suffering from said disease or condition:

Abstract: The present invention includes methods for treating a human patient with Crenolanib, wherein the human patient is suffering from a FLT3 mutated leukemia, the method comprising: determining that the human patient has a poor prognosis by: obtaining or having obtained a leukemia biological sample and performing or having performed a genotyping assay on the biological sample to determine that the human patient has both a mutated FLT3 or a constitutively active FLT3 mutant and one or more driver mutations in one or more epigenetic regulator proteins that results in a loss of normal function of the epigenetic regulator proteins which, indicates that the patient has a poor prognosis; and administering to the patient determined to have the poor prognosis a therapeutically effective amount of Crenolanib, or a pharmaceutically acceptable salt thereof having the formula: to treat the leukemia.

Abstract: The present invention includes methods for treating a proliferative disorder comprising administering a therapeutically effective amount of crenolanib or a salt thereof in combination with pharmaceutical agent targeting apoptosis pathway proteins wherein the crenolanib and other agent are provided at least one of sequentially or concomitantly in a subject for use in the treatment of the proliferative disease, wherein the subject is a human subject.

Abstract: The present invention includes methods for reducing or eliminating pain a subject comprising administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof

Abstract: The present invention includes methods for treating TRKA, TRKB, and/or TRKC driven proliferative disorder in a subject comprising administering to the subject a therapeutically effective amount of crenolanib, wherein the subject has a proliferative disorder with overexpression, activation, amplification, or mutation of TRKA, TRKB, and/or TRKC kinase.