Targeted treatment of mature t-cell lymphoma

Abstract

A method and medicament comprising 4,4,4-trifluoro-N-[(IS)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide or a pharmaceutically acceptable salt or hydrate thereof for treating aggressive peripheral T-cell lymphoma is provided.

We claim: 
     
         1 . A method of treating a patient suffering from aggressive peripheral T-cell lymphoma (PTCL), comprising administering to a PTCL not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma (ALCL), or angioimmunoblastic T-cell lymphoma (AITL) patient in need of treatment an effective amount of 4,4,4-trifluoro-N-[(1S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide, or a pharmaceutically acceptable salt or hydrate thereof,
 wherein the administering comprises:
 administering a loading dose of 75 to 150 mg/dose of 4,4,4-trifluoro-N-[(1 S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide or a pharmaceutically acceptable salt or hydrate thereof; followed by 
 administering a maintenance dose of 25 to 75 mg/dose of 4,4,4-trifluoro-N-[(1S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide or a pharmaceutically acceptable salt or hydrate thereof. 
   
     
     
         2 . The method of  claim 1 , wherein the loading dose is administered two or three times per week for at least one week of a 28 day cycle. 
     
     
         3 . The method of  claim 1 , wherein the loading dose of 4,4,4-trifluoro-N-[(1S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide or a pharmaceutically acceptable salt or hydrate thereof is administered every other day over a five day period followed by two days without administration (T.I.W.). 
     
     
         4 . The method of  claim 1 , wherein the maintenance dose is administered three times per week. 
     
     
         5 . The method of  claim 1 , wherein the maintenance dose of 4,4,4-trifluoro-N-[(1S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide or a pharmaceutically acceptable salt or hydrate thereof is administered T.I.W. 
     
     
         6 . The method of  claim 1 , wherein 2 or 3 loading doses are administered over the course of one week, or 4 to 6 loading doses are administered over the course of two weeks. 
     
     
         7 . The method of  claim 1 , wherein 8 to 12 loading doses are administered over the course of four weeks. 
     
     
         8 . The method of  claim 1 , wherein the loading dose is 75 mg/dose. 
     
     
         9 . The method of  claim 1 , wherein the maintenance dose is 50 mg/dose. 
     
     
         10 . The method of  claim 1 , wherein the loading dose is 75 mg/dose and the maintenance dose is 50 mg/dose. 
     
     
         11 . The method of  claim 1 , wherein the amounts of the loading dose and the maintenance dose are different. 
     
     
         12 . The method of  claim 1 , wherein the patient has advanced or metastatic PTCL-NOS, ALCL, or AITL. 
     
     
         13 . The method of  claim 1 , wherein the maintenance dose is administered over any remaining days of the 28 day cycle. 
     
     
         14 . The method of  claim 13 , wherein, after the maintenance dose is administered over any remaining days of the 28 day cycle, the maintenance dose is administered over one or more additional 28 day cycles. 
     
     
         15 . The method of  claim 1 , further comprising administering 1 to 50 mg/dose of a corticosteroid during administration of the loading dose. 
     
     
         16 . The method of  claim 15 , wherein the corticosteroid is selected from the group consisting of hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisone, methylprednisolone, and dexamethasone. 
     
     
         17 . The method of  claim 15 , wherein:
 2 or 3 loading doses are administered over the course of one week;   4 to 6 loading doses are administered over the course of two weeks; or   8 to 12 loading doses are administered over the course of four weeks; and/or   the maintenance dose is administered three times per week.   
     
     
         18 . The method of  claim 1 , wherein:
 2 or 3 loading doses are administered over the course of one week; or   4 to 6 loading doses are administered over the course of two weeks; or   8 to 12 loading doses are administered over the course of four weeks; and   the maintenance dose is administered three times per week.   
     
     
         19 . The method of  claim 18 , further comprising administering 1 to 50 mg/dose of a corticosteroid during administration of the loading dose. 
     
     
         20 . The method of  claim 19 , wherein the corticosteroid is selected from the group consisting of hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisone, methylprednisolone, and dexamethasone.