Dosing and administration of recombinant L-asparaginase
The present invention provides compositions and methods for treating a disease treatable by asparagine depletion in a human subject comprising dosing a human subject with L-asparaginase.
1 . A method of treating cancer in a human subject in need thereof, said method comprising administering to the human subject L-asparaginase, other than an Escherichia coli derived asparaginase, as a set of time-ordered doses;
wherein the set of time-ordered doses comprises two series of three doses, wherein a first dose and a second dose are each 25 mg/m 2 and a third dose is 50 mg/m 2 ,
wherein the first, the second and the third dose are administered on a Monday, Wednesday and Friday, respectively, and wherein the L-asparaginase is a tetramer wherein each monomer of the tetramer comprises SEO ID NO:1,
wherein the doses at 25 mg/m 2 are administered intravascularly and the doses at 50 mg/m 2 are administered intramuscularly, and
wherein the cancer is a blood cell cancer treatable by asparagine depletion, thereby treating cancer in the subject.
2 . The method of claim 1 , wherein the human subject exhibited hypersensitivity to the Escherichia coli derived asparaginase.
3 . The method of claim 1 , wherein the human subject is an adult.
4 . The method of claim 1 , wherein the human subject is pediatric.
5 . The method of claim 1 , wherein the L-asparaginase demonstrates less than 6% aggregation.
6 . The method according to claim 1 , wherein the L-asparaginase is co-administered with one or more other chemotherapeutic agents as part of a multi-agent chemotherapeutic regimen.
7 . A method of substituting a treatment of a human subject for cancer, wherein the human subject is in need thereof, said method comprising administering to the human subject, as a substitute for an Escherichia coli derived asparaginase, a series of six doses of an L-asparaginase,
wherein a first dose and a second dose are each 25 mg/m 2 and a third dose is 50 mg/m 2 ,
wherein the first, the second and the third dose are administered on a Monday, Wednesday and Friday, respectively, and
wherein the L-asparaginase is a tetramer wherein each monomer of the tetramer comprises SEO ID NO: 1
wherein the doses at 25 mg/m 2 are administered intravascularly and the doses at 50 mg/m 2 are administered intramuscularly,
wherein the L-asparaginase is not an Escherichia coli derived asparaginase, and
wherein the cancer is a blood cell cancer treatable by asparagine depletion, thereby substituting a treatment of the human subject for cancer.
8 . The method of claim 7 , wherein each respective dose of the Escherichia coli derived asparaginase in a plurality of doses of the Escherichia coli derived asparaginase is separately substituted with an instance of the series of six doses of the L-asparaginase.
9 . The method of claim 7 , wherein the human subject exhibited hypersensitivity to the Escherichia coli derived asparaginase.
10 . The method of claim 7 , wherein the human subject is an adult.
11 . The method of claim 7 , wherein the human subject is pediatric.
12 . The method of claim 7 , wherein the L-asparaginase demonstrates less than 6% aggregation.
13 . The method according to claim 7 , wherein the L-asparaginase is co-administered with one or more other chemotherapeutic agents as part of a multi-agent chemotherapeutic regimen.
14 . The method according to claim 1 , wherein the cancer is acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL).
15 . The method according to claim 1 , wherein the cancer is acute myeloid leukemia (AML).
16 . The method according to claim 1 , wherein the cancer is diffuse large B-cell lymphoma (DLBCL).
17 . The method according to claim 7 , wherein the cancer is acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL).
18 . The method according to claim 7 , wherein the cancer is acute myeloid leukemia (AML).
19 . The method according to claim 7 , wherein the cancer is diffuse large B-cell lymphoma (DLBCL).
20 . The method of claim 1 , wherein the first dose is administered on a Monday, the second dose is administered on a Wednesday, and the third dose is administered on a Friday.