Claims for Patent: 12,582,625

Summary for Patent: 12,582,625

Title:	Methods for treating neuroblastoma
Abstract:	The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.
Inventor(s):	Eugene Gerner, Elizabeth Bruckheimer, Giselle Saulnier Sholler
Assignee:	Uswm LLC , Arizona's Public Universities
Application Number:	US18/999,227
Patent Claims:	1. A method for reducing the risk of relapse of neuroblastoma in a patient diagnosed with high-risk neuroblastoma, the method comprising: orally administering to the patient a pharmaceutical composition comprising α-difluoromethylornithine (DFMO) hydrochloride monohydrate; wherein the pharmaceutical composition is orally administered to the patient twice a day, independent of the patient's food intake; wherein the oral administration of the pharmaceutical composition twice a day provides to the patient a total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate, expressed as grams α-difluoromethylornithine (DFMO) hydrochloride monohydrate per m2 body surface area, that is from 0.05 grams/m2 to 5 grams/m2; wherein the patient has demonstrated at least a partial response to prior therapy and the patient's high-risk neuroblastoma is in remission; and wherein the prior therapy comprises anti-GD2 immunotherapy. 2. The method according to claim 1, wherein the pharmaceutical composition is a powder. 3. The method according to claim 1, wherein the pharmaceutical composition is one or more tablets. 4. The method according to claim 3, wherein each of the one or more tablets comprises 250 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 5. The method according to claim 1, wherein the prior therapy further comprises chemotherapy. 6. The method according to claim 1, wherein the patient has demonstrated at least a partial response to prior therapy by demonstrating one of the following: (i) no evidence of neuroblastoma based on anatomical imaging and on pathological assessment of the bone marrow; or (ii) neuroblastoma detected on anatomical imaging that is determined to be metabolically inactive by functional imaging, and no evidence of neuroblastoma in the bone marrow based on pathological assessment of the bone marrow. 7. The method according to claim 1, wherein the patient has demonstrated a complete response to prior therapy. 8. The method according to claim 1, wherein the oral administration of the pharmaceutical composition twice a day provides to the patient a total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate that is from 1 gram/m2 to 3 grams/m2. 9. The method according to claim 1, wherein the oral administration of the pharmaceutical composition twice a day provides to the patient a total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate that is from 1 gram/m2 to 2 grams/m2. 10. The method according to claim 1, wherein the amount of α-difluoromethylornithine (DFMO) hydrochloride monohydrate administered to the patient is: 250 mg α-difluoromethylornithine (DFMO) hydrochloride monohydrate twice a day, if the patient has a body surface area that is at least 0.25 m2 and is less than 0.5 m2, 500 mg α-difluoromethylornithine (DFMO) hydrochloride monohydrate twice a day, if the patient has a body surface area that is at least 0.5 m2 and is less than 0.75 m2, 750 mg α-difluoromethylornithine (DFMO) hydrochloride monohydrate twice a day, if the patient has a body surface area that is at least 0.75 m2 and is no greater than 1.5 m2, and 1 gram α-difluoromethylornithine (DFMO) hydrochloride monohydrate twice a day, if the patient has a body surface area that is greater than 1.5 m2. 11. A method for reducing the risk of relapse of neuroblastoma in a patient diagnosed with high-risk neuroblastoma, the method comprising: orally administering to the patient a total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate, expressed as grams α-difluoromethylornithine (DFMO) hydrochloride monohydrate per m2 body surface area, that is from 0.05 grams/m2 to; 5 grams/m2; wherein the patient has demonstrated at least a partial response to prior therapy and the patient's high-risk neuroblastoma is in remission; and wherein the prior therapy comprises anti-GD2 immunotherapy. 12. The method according to claim 11, wherein the total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is from 1 gram/m2 to 2 grams/m2. 13. The method according to claim 12, wherein the α-difluoromethylornithine (DFMO) hydrochloride monohydrate is orally administered to the patient in one or more tablets. 14. The method according to claim 13, wherein each of the one or more tablets comprises 250 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 15. The method according to claim 12, wherein the α-difluoromethylornithine (DFMO) hydrochloride monohydrate is mixed with a liquid or with food prior to said oral administration. 16. The method according to claim 11, wherein the total daily dose of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is orally administered to the patient in two doses of α-difluoromethylornithine (DFMO) hydrochloride monohydrate, wherein said two doses are equal to each other, each being from 0.5 grams/m2 to 1 gram/m2 of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 17. The method according to claim 16, wherein each of said two doses of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is administered in one or more tablets. 18. The method according to claim 17, wherein the one or more tablets each provide 250 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 19. The method according to claim 17, wherein the prior therapy further comprises chemotherapy. 20. The method according to claim 16, wherein the α-difluoromethylornithine (DFMO) hydrochloride monohydrate is mixed with a liquid or with food prior to said oral administration. 21. The method according to claim 16, wherein the prior therapy further comprises chemotherapy. 22. The method according to claim 11, wherein an amount of 250 mg, 500 mg, 750 mg, or 1000 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is administered to the patient twice a day, and wherein the prior therapy further comprises chemotherapy. 23. The method according to claim 22, wherein said amount of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is administered in one or more tablets that each provide 250 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 24. A method for reducing the risk of relapse of neuroblastoma in a patient diagnosed with high-risk neuroblastoma, the method comprising: orally administering to the patient a total amount of 250 mg, 500 mg, 1,000 mg, 1,500 mg, or 2,000 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate per day; and wherein the patient has demonstrated at least a partial response to prior therapy and the patient's high-risk neuroblastoma is in remission. 25. The method according to claim 24, wherein the prior therapy comprises anti-GD2 immunotherapy. 26. The method according to claim 25, wherein 500 mg, 1,000 mg, 1,500 mg, or 2,000 mg is the total amount of α-difluoromethylornithine (DFMO) hydrochloride monohydrate per day, and the α-difluoromethylornithine (DFMO) hydrochloride monohydrate is administered to the patient twice a day in one or more tablets. 27. The method according to claim 26, wherein the one or more tablets each provide 250 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate. 28. The method according to claim 24, wherein 500 mg, 1,000 mg, 1,500 mg, or 2,000 mg is the total amount of α-difluoromethylornithine (DFMO) hydrochloride monohydrate per day, and 250 mg, 500 mg, 750 mg, or 1,000 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate is administered to the patient twice a day to provide said total amount per day. 29. The method according to claim 24, wherein 500 mg, 1,000 mg, 1,500 mg, or 2,000 mg is the total amount of α-difluoromethylornithine (DFMO) hydrochloride monohydrate per day, and wherein for a time period of up to two years, said total amount per day is administered to the patient as 250 mg, 500 mg, 750 mg, or 1,000 mg of α-difluoromethylornithine (DFMO) hydrochloride monohydrate twice a day. 30. The method according to claim 24, wherein the prior therapy comprises anti-GD2 immunotherapy and chemotherapy.