INJECTABLE MELPHALAN COMPOSITIONS COMPRISING A CYCLODEXTRIN DERIVATIVE AND METHODS OF MAKING AND USING THE SAME

1 . A method of treating a subject suffering from a neoplastic disorder, the method comprising:

diluting a composition with an aqueous diluent to provide a dilute pharmaceutical composition comprising melphalan and a cyclodextrin derivative of formula I:

wherein n is 4, 5 or 6;

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently —H, a straight-chain or branched C 1 -C 8 -(alkylene)-SO 3 − group, or an optionally substituted straight-chain or branched C 1 -C 6 group;

wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 is a straight-chain or branched C 1 -C 8 -(alkylene)-SO 3 − group;

wherein the cyclodextrin derivative is present in the composition in a weight ratio of at least 50:1 (w/w) relative to the melphalan; and

administering the dilute pharmaceutical composition, by injection to the subject in need thereof.

2 . The method of claim 1 , wherein the neoplastic disorder is selected from: myeloma, Multiple myeloma, melanoma, acute myelogenous leukemia, malignant melanoma, breast cancer, ovarian cancer, testicular cancer, advanced prostate cancer, a neuroendocrine cancer, metastatic melanoma, a metastatic neuroendocrine tumor, a metastatic adenocarcinoma tumor, hepatocellular carcinoma, osteogenic sarcoma, polycythemia veraplasma; plasma cell neoplasm, amyloidosis, scleromyxedema, and combinations thereof.

3 . The method of claim 2 , wherein the neoplastic disorder is multiple myeloma and the administering is systemic and provides, palliative treatment of the multiple myeloma.

4 . (canceled)

5 . The method of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently a straight-chain or branched C 1 -C 8 -(alkylene)-SO 3 − group having a degree of substitution of 4 to 8 per cyclodextrin derivative, and the remaining substituents are —H.

6 . The method of claim 1 , wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 is substituted with a straight-chain C 4 -(alkylene)-SO 3 − group.

7 . The method of claim 1 , wherein the cyclodextrin derivative is a compound of formula II

wherein R is H or —(CH 2 ) 4 —SO 3 − Na + .

8 . The method of claim 1 , wherein the dilute pharmaceutical composition is substantially free of an alcohol.

9 . The method of claim 1 , wherein the aqueous diluent is a saline solution.

10 . (canceled)

11 . The method of claim 1 , wherein the melphalan in the dilute pharmaceutical composition degrades by 2% or less at about 25° C. within 0.5 hours after the diluting or by 4% or less at 25° C. within 10 hours after the diluting.

12 . The method of claim 1 , wherein the dilute pharmaceutical composition is stored about 0.5 hours to about 18 hours prior to the administering.

13 . The method of claim 1 , wherein the administering, provides a melphalan C max in the subject suffering from a neoplastic disorder that is at least 20% or greater than a melphalan C max provided by a melphalan formulation containing an equivalent dose of melphalan and lacking the cyclodextrin derivative.

14 . The method of claim 1 , wherein the administering provides a melphalan AUC 0-t in the subject suffering from a neoplastic disorder that is at least 20% or greater than a melphalan AUC 0-t provided by a melphalan formulation containing an: equivalent dose of melphalan and lacking the cyclodextrin derivative.

15 - 42 . (canceled)

43 . The method according to claim 1 , wherein the cyclodextrin derivative is a sulfoalkyl ether-beta-cyclodextrin and the weight ratio of sulfoalkyl ether-beta-cyclodextrin to melphalan is from 50:1 to 100:1.

44 . The method according to claim 1 , wherein the cyclodextrin derivative is a sulfoalkyl ether-beta-cyclodextrin and the weight ratio of sulfoalkyl ether-beta-cyclodextrin to melphalan is about 54:1.

45 . The method according to claim 1 , wherein the composition comprises 25 mg to 125 mg melphalan.

46 . The method according to claim 1 , wherein the melphalan is a hydrochloride salt of melphalan.

47 . The method according to claim 1 , wherein the composition is a solid pharmaceutical composition.

48 . The method according to claim 47 , wherein the solid pharmaceutical composition is a powder.

49 . The method according to claim 47 , wherein the solid pharmaceutical composition is a lyophilized powder.