Compositions and methods for treating lymphoma
View Patent ↗This invention provides methods for treating neoplasias in a mammal. In particular, the invention provides methods for treating various types of lymphomas, including relapsed forms of non-Hodgkin's Lymphoma. These methods involve the administration of liposome-encapsulated vinca alkaloids, e.g., vincristine, to a mammal with a lymphoma.
1. A method for treating a cancer selected from the group consisting of lymphoma, leukemia and myeloma in a human, said method comprising administering to said human a composition comprising liposome-encapsulated vincristine at a dosage of about 1.5 mg/m 2 to about 2.4 mg/m 2 , wherein the liposome comprises sphingomyelin and cholesterol in a ratio of about 75/25 (mol % sphingomyelin/mol % cholesterol) to about 50/50 (mol % sphingomyelin/mol % cholesterol) and vincristine at a concentration of about 0.10-0.50 mg/ml.
2. A method for treating lymphoma, leukemia or myeloma in a human, said method comprising administering to said human a composition comprising liposome-encapsulated vincristine at a dosage of at least about 2.0 mg/m 2 to about 2.4 mg/m 2 , wherein the liposome comprises sphingomyelin and cholesterol in a ratio of about 55/45 (mol % sphingomyelin/mol % cholesterol) and vincristine at a concentration of about 0.10-0.50 mg/ml.
3. The method of claim 1 or 2 , wherein the liposome-encapsulated vincristine comprises vincristine at a concentration of about 0.15 to about 0.20 mg/ml.
4. The method of claim 1 or 2 , wherein the liposome-encapsulated vincristine comprises vincristine at a concentration of about 0.16 mg/ml.
5. The method of claim 1 , wherein the liposome-encapsulated vincristine is administered to the human at a dose of about 2.0 mg/m 2 to about 2.4 mg/m 2 .
6. The method of claim 1 or 2 , wherein the lymphoma, leukemia or myeloma relapsed or refractory.
7. The method of claim 1 or 2 , wherein the lymphoma is non-Hodgkin's lymphoma (NHL).
8. The method of claim 1 or 2 , wherein the leukemia is Acute Lymphocytic Leukemia (ALL).
9. The method of claim 1 , wherein the liposomes comprise sphingomyelin and cholesterol in a ratio of about 70/30 (mol % sphingomyelin/mol % cholesterol) to about 55/45 (mol % sphingomyelin/mol % cholesterol).
10. The method of claim 1 , wherein the liposomes comprise sphingomyelin and cholesterol in a ratio of about 55/45 (mol % sphingomyelin/mol % cholesterol).
11. The method of claim 1 or 2 , wherein said liposome-encapsulated vincristine is administered parenterally.
12. The method of claim 1 or 2 , wherein said liposome-encapsulated vincristine is administered systemically by intravenous infusion.
13. The method of claim 12 , wherein the liposome-encapsulated vincristine is administered to the human by intravenous infusion over about 30 to about 90 minutes.
14. The method of claim 12 , wherein the liposome-encapsulated vincristine is administered to the human 1 by intravenous infusion over about 60 minutes.
15. The method of claim 12 , wherein the liposome-encapsulated vincristine is administered to the human intravenously over about 60 minutes about every 7 to about 21 days.
16. The method of claim 12 , wherein the liposome-encapsulated vincristine is administered to the human about every 1 to about 28 days.
17. The method of claim 1 or 2 , wherein the liposome-encapsulated vincristine is administered to the human about every 7 to about 21 days.
18. The method of claim 1 or 2 , wherein the liposome-encapsulated vincristine is administered to the human about every 14 days.
19. The method of claim 1 or 2 , wherein the liposome-encapsulated vincristine is administered to the human about every 7 days.
20. The method of claim 1 or 2 , wherein said liposome-encapsulated vincristine is co-administered with at least one additional cancer therapy.
21. The method of claim 20 , wherein said additional cancer therapy is selected from the group consisting of radiation therapy, bone marrow transplantation, hormone therapy, surgery, cyclophosphamide, doxorubicin, prednisone, a taxane, a camptothecin, a podophyllins, and combinations thereof.
22. The method of claim 20 , wherein said additional cancer therapy is an anti-tumor antibody.
23. The method of claim 20 , wherein said additional cancer therapy is an antisense drug or an anti-tumor vaccine.
24. The method of claim 1 or 2 , wherein said liposome-encapsulated vincristine is co-administered with a treatment for neurotoxicity.
25. The method of claim 1 or 2 , wherein about 3.0 to about 6.0 mg of vincristine is administered to the human.
26. The method of claim 20 , wherein said additional cancer therapy is a taxane.
27. The method of claim 26 , wherein said taxane is a liposomal taxane.
28. The method of claim 1 , wherein said vincristine is vincristine sulfate.
29. The method of claim 1 or 2 , wherein said liposomal-encapsulated vincristine is co-administered with cyclophosphamide, doxorubicin and prednisone.
30. The method of claim 2 , further comprising the steps of:
(a) mixing a first solution comprising 1 mg/ml to 5 mg/ml vincristine sulfate at a pH of 3.5 to 5.5 with a second solution comprising empty liposomes in a buffer at a pH of about 4.0, wherein the liposomes comprise sphingomyelin and cholesterol in a ratio of about 55/45 (mol % sphingomyelin/mol % cholesterol); and
(b) adding a third solution comprising an alkaline phosphate buffer having a pH sufficient to raise the pH of said mixture prepared in step (a) to produce said liposome-encapsulated vincristine prior to administration to said human.