Patent EA-004107-B1 (EA)
Title: Combination therapies for b-cell lymphomas comprising administration of anti-cd20 antibody
Inventor: GRILLO-LOPEZ ANTONIO
IPC: C02F1/00
Filed: 1999-08-11
Abstract: 1. A method for treating B-cell lymphoma including administering a synergetic therapeutic combination, which comprises at least one anti-CD20 antibody and at least one cytokine, wherein the therapeutic effect is better than the additive effects of either therapy administered alone. 2. The method of claim 1, wherein at least one cytokine is selected from the group consisting of alpha interferon, gamma interferon, IL-2, GM-CSF and G-CSF. 3. The method of claim 1, wherein said anti-CD20 antibody and said alpha interferon, gamma interferon, IL-2, GM-CSF or G-CSF is administered sequentially, in either order, or in combination. 4. The method of claim 1, wherein said anti-CD20 antibody is a chimeric antibody. 5. The method of claim 4, wherein said chimeric anti-CD20 antibody is C2B8(Rituximab(RTM)). 6. A method for treating B-cell lymphoma comprising administering to a patient a synergetic combination, which comprises a therapeutically effective amount of anti-CD20 antibody and at least one chemotherapeutic agent, wherein said method provides destruction of B-cell lymphoma with synergetic effect exceeding the one that achieves by using anti-CD20 antibody and chemotherapeutic agent alone. 7. The method of claim 6 comprising destruction of B-cell lymphoma in a patient with chemotherapeutic agent dose, which would not be sufficient for destruction of B-cell lymphoma if it's administered alone. 8. The method of claim 6 comprising destruction of B-cell lymphoma in a patient, resistant to chemotherapeutic agent, which is administered alone. 9. The method of claim 6, wherein said anti-CD20 antibody and said at least one chemotherapeutic agent are administered in sequence in any order or combination. 10. The method of claim 6, wherein said chemotherapeutic agent comprises fludarabine. 11. The method of claim 6, wherein said chemotherapeutic agent comprises a combination of cyclophosphoramide, doxorubicine, vinchristine and prednisone. 12. The method of claim 6, wherein said chemotherapy is selected from the group consisting of CHOP, ICE, mitozantrone, cytarabine, DVP, ATRA, idarubicin, Hoelzer chemotherapy regime, La La chemotherapy regime, ABVD, CEOP, 2-CdA, FLAG & IDA with or without subsequent G-CSF treatment, VAD, M & P, C-Weekly, ABCM, MOPP and DHAP. 13. The method of claim 6, wherein said anti-CD20 antibody is a chimeric antibody. 14. The method of claim 13, wherein said chimeric antibody is C2B8(Rituximab(RTM)). 15. The method of claim 6 comprising an effect of anti-CD20 antibody during chemotherapeutic regime. 16. The method of claim 15 comprising an effect of anti-CD20 antibody during CHOP regime. 17. The method of claim 16 for treating patients with non-Hodgkin's lymphoma (NHL), 18. A method of reducing residual of B-cell disease in a patient receiving bone marrow or stem cells after myeloablative therapy by administering to said patient an anti-CD20 antibody, effective for reducing a number of CD20 antigen-expressive cells and for reducing residual of B-cell disease in a patient. 19. The method of claim 18, wherein said anti-CD20 antibody comprises human IgGI permanent areas. 20. The method of Claim 18, wherein said antibody is a chimeric anti-CD20 antibody. 21. The method of Claim 18, wherein said antibody is C2B8(Rituximab(RTM)). 22. The method of Claim 18, wherein treated patient has B-cell lymphoma. 23. The method of Claim 22, wherein said B-cell lymphoma is selected from the group consisting of low grade/follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL), high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noncleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom's Macroglobulinemia. 24. The method of claim 20, wherein a treated subject has low grade, intermediate grade and high grade lymphoma. 25. The method of claim 20, wherein a treated subject has I, II, III or IV stage of non-Hodgkin's lymphoma (NHL). 26. The method of claim 20, wherein myeloablative therapy is effected by using Y2B8. 27. The method of claim 20, wherein said treated patient has a relapse after myeloablative therapy. 28. The method of claim 18 comprising at least one chemotherapeutic agent. 29. The method of claim 19, wherein said agent of anti-CD20 antibody is C2B8, which is administered in a dose within 10-500 mg/m2. 30. The method of claim 29, wherein an antibody is administered by means of infusion. 31. The method of claim 29, wherein a dose is about 375 mg/m2. 32. The method of claim 31, wherein said dose of an antibody is administered weekly. 33. The method of claim 1, wherein said B-cell lymphoma is selected from the group consisting of low grade/follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL), high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noncleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom's Macroglobulinemia. 34. The method of claim 1, wherein said B-cell lymphoma is selected from the group consisting of low grade/follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL), high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noncleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom's Macroglobulinemia.