AU784971B2 - Treatment of patients having non-Hodgkins lymphoma with bone marrow involvement with anti-CD20 antibodies - Google Patents
Treatment of patients having non-Hodgkins lymphoma with bone marrow involvement with anti-CD20 antibodies Download PDFInfo
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Description
WO 01/10462 PCT/US00/40459 Treatment of Patients having Non-Hodgkins Lymphoma with Bone Marrow Involvement with Anti-CD20 Antibodies Field of the Invention The present invention relates to a method of reducing the number of cancerous B cells in the bone marrow of a patient having a B cell lymphoma prior to radioimmunotherapy comprising administration of an antiantibody. Combined therapeutic methods of treating a patient having lymphoma with associated bone marrow involvement are also encompassed.
Background of the Invention Radioimmunotherapy of B cell lymphoma is limited by marrow involvement, infiltration of the bone marrow by cancerous B lymphocytes. This complicates radioimmunotherapy in two regards: antibody binding to diseased cells in the marrow will deliver a dose of radiation to the marrow thereby causing unwanted myelosuppression; and marrow crowding of normal cells and progenitors will weaken healthy marrow reserves so that patients may actually be closer to grade 3 or 4 cytopenias than would be the case in patients without marrow involvement. In either case, the patient may be less tolerant to radioimmunotherapy, with B cell depleting antibody conjugated to a radioisotope such as 9"Y or As a consequence, patients with greater than 25% bone marrow involvement P QPERVAR\PECIk726DX) I spa do.2102A)6 -2are generally excluded from treatment with radioimmunotherapy.
As found by Wiseman and colleagues, the clinical parameters of baseline platelet counts and degree of bone marrow involvement are accurate predictors of hematologic toxicity in patients with low-grade follicular non-Hodgkins lymphoma undergoing therapy with Y2B8, a murine antibody conjugated to 0 Y. For instance, eight percent of patients (2/25) without bone marrow involvement developed Grade 4 thrombocytopenia vs. 25% of those with 0.1-5% bone marrow involvement. 45% (5/11) of those with 5-20% involvement, and 100% with 20-25% involvement (Wiseman et al. IDEC-Y2B8 radioimmunotherapy: baseline bone marrow involvement and platelet count are better predictors of 15 hematologic toxicity than dosimetry. Blood 1998 Supplement November, 92(10) 417a (1721) Poster Board #/Session: 393-
III).
It would be useful to develop methods of reducing the bone marrow involvement in patients with non-Hodgkin's 20 lymphoma such that these patients may benefit from new radioimmunotherapies, thereby providing another avenue of treatment and decreasing the chance of relapse.
Summary of the Invention The present invention relates to methods of treating patients having B cell lymphoma accompanied by bone marrow involvement comprising administering a monoclonal antibody or fragment thereof such that said bone marrow involvement is reduced or alleviated. Specifically, the invention encompasses methods of reducing the number of cancerous B 16-06-'06 15:25 FROM- T-004 P008/079 F-884 r:tiyW4XKr8CO2HOCsa a uPrnane4ac4 -3cells in the bone marrow of a patient having non-Hodgkin's lymphoma prior to radioimmunotherapy comprising administering to said patient an effective amount of a therapeutic antibody. The methods are also useful for reducing bone marrow involvement prior to administration of antibodies labeled with cytotoxic moieties such as toxins, or any immunotherapeutic which could damage healthy bone marrow progenitors by virtue of their location in the vicinity of targeted cells which have infiltrated the bone marrow.
According to one embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount S" 15 of an anti-CD20 antibody or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that binds to B cell 20 lymphoma cells, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patent having bone marrow involvement greater than According to another embodiment of the invention there is provided the use of a B cell depleting anti-CD20 antibody or a B cell depleting fragment thereof for the manufacture of a medicament for reducing the number of cancerous B cells COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:25 FROM- T-004 P009/079 F-884 -3Ain the bone marrow of a patient having non-Hodgkin's lymphoma with greater than 25% bone marrow involvement prior to radioimmunotherapy with a cytotoxic radiolabeled antibody that binds to B cell lymphoma cells.
According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone ~marrow involvement to less than 25%, and then administering *to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that binds to a B cell lymphoma cell antigen selected from 15 CD19 and wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow a. involvement is lower than that which is associated with a 20 administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:25 FROM- T-004 P010/079 F-884 -3Bto the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled anti-CD19 antibody that is radiolabeled with wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled anti-CD19 antibody that is radiolabeled with 20 wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:26 FROM- T-004 P011/079 F-884 P ~rflJXR'mICri2t>WO2 ablaflea-MMt -3Cfragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that is radiolabeled with "Y, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow 15 involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering Sto the patient having less than 25% bone marrow involvement 20 an effective amount of the S"Y-labeled anti-CD20 antibody Y2B8, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than According to a further embodiment of the present invention there is provided a method for treating a patient having B cell lymphoma with greater than 25% bone marrow COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:26 FROM- T-004 P012/079 F-884 P.AOPHM1tW TkSOWO-2al *aaniebftO-&Um -3Dinvolvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that is radiolabeled with 1311, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled 10 antibody to the patient having less than 25% bone marrow ~involvement is lower than that which is associated with 0 administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than Preferably, anti-CD20 antibodies are used, although antibodies to other B cell surface markers may also be used, anti-CD19 antibodies. The cell surface protein which is targeted should have the characteristics of being expressed mainly on cancerous B cells and not generally on 0.0.
normal cells or B cell precursors, and preferably does not 20 shed, internalize or modulate upon being bound by antibody.
The term antibody "fragments" includes any *0* therapeutically effective portion or derivative of a therapeutic antibody, which is effective to bind to the intended target and produce the intended result. Included are Fab, fragments, Fab fragments, Fv fragments, domaindeleted antibodies, etc. Preferably, the antibodies used in the present invention are human, COMS ID No: SBMI-03899250 Received by IP Australia: lime 15:59 Date 2006-06-16 16-06-'06 15:26 FROM- T-004 P013/079 F-884 P tP R KnSfCM bOROOSC c'o..lA-l. 'X -4chimeric or humanized antibodies, such that the antibodies contain human constant region domains capable of stimulating human effector functions. A preferred antibody is the chimeric anti-CD20 antibody, rituximab (marketed as RITUXAN® in the U.S. and MABTHERA® in Britain).
The patients who will most benefit from the present invention will be patients who have greater than 25t bone marrow involvement before being treated with the disclosed immunotherapy. Such patients may be identified by prior diagnostic imaging using antibodies radiolabeled with gammaemitting isotopes such as Such patients may also be identified following bone marrow biopsy.
99* According to a study by Wiseman et al., such patients have a very high chance of developing thrombocytopenia due 15 to radioimmunotherapy. However, as the chance of developing such an adverse reaction following radioimmunotherapy increases depending on the extent of bone marrow gi* involvement, any patient with any level of bone marrow involvement will benefit from the present invention in that 20 they will benefit from a decreased risk of *999 radioimmunotherapy-induced thrombocytopenia following the disclosed treatment.
9 9 The dosages to be used in the present invention may vary depending on the patient, the extent of bone marrow involvement, and the antibody used. Chimeric antibody such as rituximab may be administered at a dosage of at least about 50 mg/m 2 weekly for at least 4 COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 WO 01/10462 PCT/USOO/40459 weeks. A preferred dosage regimen is about 375 mg/m 2 weekly for four weeks.
Because the purpose of the methods of the present invention is to decrease the bone marrow involvement in patients with lymphoma preparing to undergo radioimmunotherapy, the treatment methods of the present invention naturally encompass treatment with a radiolabeled antibody subsequent to purging of the marrow.. The radiolabeled antibody may also be directed to any B cell surface marker which is found generally on cancerous cells and not normal cells. Preferably, the radiolabeled antibody is an anti-CD20 antibody.
Preferred radiolabels are beta emitting isotopes such as 90 Y or 13'I, but any radioisotope may be used so long as it may be effectively conjugated to the antibody, it has a relatively short decay range, and it succeeds in killing nearby cells, the cells to which it is targeted. A preferred radiolabeled antiantibody is Y2B8.
A patient should generally be treated within one week after administration of the depleting antibody, so long as they are not severely cytopenic, platelets <150,000. If the patient is cytopenic following treatment with the depleting antibody, recovery should be allowed to occur, e.g. nadir AGC >1000 or platelets >150,000, before radioimmunotherapy. In cases where cell recovery in the peripheral blood and/or bone marrow is permitted to occur, more depleting antibody may be administered directly before immunotherapy. Such a WO 01/10462 PCT/US00/40459 -6secondary dosage may be administered, for example, at about 250 mg/m 2 for about two weeks directly before or overlapping with radioimmunotherapy.
Dosages of radiolabeled antibodies will also vary depending on the patient, the antibody specificity, half-life, stability, etc., and of course, the extent of disease. Radiolabeled anti-CD20 antibodies like Y2B8 are administered at a dosage of about 0.1 to 0.5 mCi/kg.
It. should be clear that the treatment methods disclosed herein may be combined with other known treatment methods such as chemotherapy or radiotherapy.
Bone marrow or peripheral blood stem cells may be harvested from said patient subsequent to treatment with antibody and prior to treatment with said radiolabeled antibody in order to effect autologous bone marrow or stem cell transplantation after radiotherapy.
It may also be useful to treat patients with cytokines in order to upregulate the expression of pr other target protein on the surface of cancerous B cells prior to administration of the depleting antibody or the radiolabeled antibody. For upregulation of cytokines useful for this purpose are IL-4, GM-CSF and TNF-alpha. Cytokines may also be administered simultaneously with or prior to or subsequent to administration of the depleting antibody or radiolabeled antibody in order to stimulate immune effector functions. Cytokines useful for this purpose include interferon alpha, GM-CSF and G-CSF.
16-06-'06 15:26 FROM- T-004 P014/079 F-884 -7- Chemotherapeutic regimens may be used to supplement the therapies disclosed herein, and may be administered simultaneously with or sequentially in any order with administration of said radiolabeled antibody. The chemotherapy regimen may be 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. A preferred chemotherapeutic regimen is CHOP.
The methods of the present invention may be used to treat a variety of B cell lymphomas but are particularly useful wherein said B cell lymphoma is non-Hodgkin's lymphoma (NHL). Rituximab has already been approved for the treatment of low-grade-follicular NHL, but the present inventors have surprisingly found that rituximab is also beneficial for the treatment of intermediate- and high-grade NHL, including bulky disease. Accordingly, the lymphomas which are treatable by the methods of the present invention include 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, so long as such lymphomas are accompanied by bone marrow involvement which complicates the availability of radioimmunotherapy.
COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:27 FROM- T-004 P015/079 F-884 -8- Exemplary treatment conditions will now be illustrated by way of the following data.
Radioimmunotherapy of Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL): Y2B8 Phase I/II "Y Trial This Phase I/II trial included 58 relapsed or refractory NHL patients, median age 60, 43% bone marrow involvement, 60% bulky lesions 5 cm (White et al. Poster Presentation at VII International Conference on Malignant Lymphoma, Lugano, Switzerland. Annals of Oncology Suppl. 3 (1999) 10:64 All patients had dosimetry by gamma camera measurements and by serial urine and blood sampling S: following administration of 5 mCi of "In-labeled antibody In2B8. Prior to imaging and therapy, rituximab was used to 15 clear peripheral B-cells and optimize radiolabeled antibody distribution. One week later, Y2B8 0.3 or 0.4 mCi/kg) was administered to Group 2 3 patients. No bone marrow or stem cell harvest was performed.
0** 20 Results: The MTD was 0.4 mCi/kg (0.3 mCi/kg for patients with mild thrombocytopenia). Adverse events were mainly hematologic, transient and reversible. Overall, 5 patients developed nadir platelet counts <10,000/mm 3 and 14 patients developed nadir AGC <500. Three patients acquired infections requiring COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 P %0PERV hpPEC1k626 I -cdwu do-2MIAJ2 -9hospitalization over a one year observation period.
Only 2% developed HAMA/HACA. Mean serum immunoglobulins remained normal over a one year observation period. The ORR was 67% (26% CR and 41% PR) in all histologies and 82% for patients with low-grade NHL. The median TTP was 12.9+ months for responders, and the duration of response was 11.7+ months as projected by Kaplan Meier methodology. In patients with baseline splenomegaly, 4/8 patients responded compared to 74% (29/39) without splenomegaly 0.1761). Two clinical parameters, baseline platelet counts and degree of bone marrow involvement in baseline biopsy, were better at predicting severity of hematologic toxicity than dosimetry parameters.
Throughout this specification and the claims which 15 follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of 20 integers or steps.
The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia.
Claims (18)
16-06-'06 15:27 FROM- T-004 P016/079 F-884 THE CLAIMS DEFINRING THE INVENTION ARE AS FOLLOWS: 1. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of an anti- antibody or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that binds to B cell lymphoma cells, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with 15 administering the cytotoxic radiolabeled antibody to the patent having bone marrow involvement greater than 99* 2. The method of claim 1, wherein said anti-CD20 antibody is a human, chimeric or humanized antibody. 99: 9 9 999o 3. The method of claim 2, wherein said anti-CD20 antibody is a chimeric anti-CD20 antibody. 9 9 4. The method of claim 3, wherein said chimeric antibody is rituximab. COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 P QOPER.kRMSPECl76260-0-lIspa cnd,,, do 2IAJ2A6 -11- The method of claim 4, wherein said chimeric antibody is administered at a dosage of at least about mg/m 2 weekly for at least 4 weeks. 6. The method of claim 5, wherein said chimeric antibody is administered at a dosage of about 375 mg/m 2 weekly for four weeks. 7. The method of claim 1, wherein said radiolabeled antibody is an anti-CD20 antibody. 8. The method of claim 7, wherein said radiolabeled anti-CD20 antibody is Y2B8. 15 9. The method of claim 8, wherein said radiolabeled anti-CD20 antibody is administered at a dosage of about 0.1 to 0.5 mCi/kg. 10. The method of claim 1, wherein additional 20 antibody is administered simultaneously with or sequentially Sin either order with said radiolabeled antibody. O a a 11. The method of claim 10, wherein at least a single dosage of said additional anti-CD20 antibody is administered at a dosage of about 250 mg/m 2 12. The method of claim 1, wherein bone marrow or peripheral blood stem cells are harvested from said patient subsequent to treatment with anti-CD20 antibody and prior to treatment with said radiolabeled antibody. P OPERVARSPECR7626& I spa -ftwts doc.2I21Z)6 -12- 13. The method of claim 1, wherein expression of CD20 is upregulated on the surface of cancerous B cells prior to administration of said anti-CD20 antibody by administering at least one cytokine. 14. The method of claim 13, wherein said cytokine is selected from the group consisting of IL-4, GM-CSF and TNF-alpha. The method of claim 1, further comprising treatment with a chemotherapeutic regimen simultaneously with or sequentially in any order with administration of said radiolabeled antibody. 16. The method of claim 15, 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, 20 2-CdA, FLAG IDA (with or without subsequent G-CSF treatment), VAD, M P, C-Weekly, ABCM, MOPP and DHAP. i 17. The method of claim 16, wherein the chemotherapeutic regimen is CHOP.
18. The method of claim 1, further comprising administration of at least one cytokine simultaneously with or sequentially in either order with said antibody. 16-06-'06 15:27 FROM- T-004 P017/079 F-884 p lmWSKn nC42WW-2fh w amedc-WC64W 13-
19. The method of claim 18, wherein said at least one cytokine is selected from the group consisting of interferon alpha, GM-CSF and G-CSF.
20. The method of claim 1, wherein said B cell lymphoma is non-Hodgkin's lymphoma (NHL).
21. The method of claim 20, wherein said NHL 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.
22. The use of a B cell depleting anti-CD20 antibody or a B cell depleting fragment thereof for the manufacture of a 20 medicament for reducing the number of cancerous B cells in the bone marrow of a patient having non-Hodgkin's lymphoma with greater than 25% bone marrow involvement prior to radioimmunotherapy with a cytotoxic radiolabeled antibody that binds to B cell lymphoma cells.
23. Use according to claim 22, wherein said antibody is a human antibody, a chimeric antibody or a humanized antibody. COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:27 FROM- T-004 P018/079 F-884 -14-
24. Use according to claim 23, wherein said chimeric antibody is rituximab. Use according to claim 24, wherein said chimeric anti-CD20 antibody is administered at a dosage of at least about 50 mg/m 2 weekly for at least 4 weeks.
26. Use according to claim 25, wherein said chimeric antibody is administered at a dosage of about 375 mg/m' weekly for four weeks.
27. Use according to claim 22, wherein said radiolabeled antibody is an anti-CD20 antibody.
28. Use according to claim 27, wherein said radiolabeled antibody is Y2B8.
29. A method according to claim 1, substantially as hereinbefore described with reference to the Phase I/II 20 trial.
30. Use according to claim 22, substantially as hereinbefore described with reference to the Phase I/II trial.
31. The method of claim 1, wherein the radiolabeled antibody is radiolabeled with "Y or "II.
32. The method of claim 1, wherein the radiolabeled antibody is an anti-CD19 antibody. COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:28 FROM- T-004 P019/079 F-884 nsmtsomdidw0 W
33. The method of claim 1, wherein the radiolabeled antibody is an anti-CD19 antibody that is radiolabeled with
34. The method of claim 1, wherein the radiolabeled antibody is an anti-CD19 antibody that is radiolabeled with
1311. 35. The method of claim 1, wherein the radiolabeled antibody is an anti-CD20 antibody that is radiolabeled with 15 36. The method of claim 1, wherein the radiolabeled antibody is an anti-CD20 antibody that is radiolabeled with 131 I. 37. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody that is 20 radiolabeled with 9 "Y or 1 "I. *38. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an anti-CD19 antibody. 39. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an anti-CD19 antibody that is radiolabeled with COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:28 FROM- T-004 P020/079 F-884 papeRfIaKXISPECM62*&41frtap. Mcu«a lO6I -16- The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an anti-CD19 antibody that is radiolabeled with 311I. 41. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an antibody. 42. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an antibody that is radiolabeled with 0Y. 43. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is the "Y-labeled 15 anti-CD20 antibody Y2B8. 44. The method of claim 1, wherein said anti-CD20 antibody is rituximab and the radiolabeled antibody is an antibody that is radiolabeled with 131. 45. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled antibody that binds to a B cell lymphoma cell antigen selected from CD19 and COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 200606-16 16-06-'06 15:28 FROM- T-004 P021/079 F-884 -17- wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than 46. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of 15 a cytotoxic radiolabeled anti-CDl9 antibody that is radiolabeled with wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow 20 involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than 47. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:28 FROM- T-004 P022/079 F-884 P: fRWMftlOWCfhMdOO2la cmanudw.x-6 -18- a cytotoxic radiolabeled anti-CD19 antibody that is radiolabeled with 13'I, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than 48. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled anti-CD20 antibody that is radiolabeled with "Y, wherein the risk of developing thrombocytopenia 20 associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than 49. A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising administering to the patient an effective amount of the antibody rituximab or fragment thereof that reduces the patient's lymphoma bone marrow involvement to COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:29 FROM- T-004 P023/079 F-884 ,Psacx'KfWl7eCaTZ4D* mnmaimul.I&Q&C -19- less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of the 90 Y-labeled anti-CD20 antibody Y2B8, wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than A method for treating a patient having B cell lymphoma with greater than 25% bone marrow involvement, comprising S. administering to the patient an effective amount of the anti-CD20 antibody rituximab or fragment thereof that 15 reduces the patient's lymphoma bone marrow involvement to less than 25%, and then administering to the patient having less than 25% bone marrow involvement an effective amount of a cytotoxic radiolabeled anti-CD20 antibody that is radiolabeled with 1311, 20 wherein the risk of developing thrombocytopenia associated with administering the cytotoxic radiolabeled antibody to the patient having less than 25% bone marrow involvement is lower than that which is associated with administering the cytotoxic radiolabeled antibody to the patient having marrow involvement greater than COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16 16-06-'06 15:29 FROM- T-004 P024/079 F-884 51. A method according to any one of claims 45 to substantially as hereinbefore described with reference to the Phase I/II trial. DATED this 16th day of June, 2006 Biogen Idec Inc. By DAVIES COLLISON CAVE Patent Attorneys for the Applicant o e ***ee COMS ID No: SBMI-03899250 Received by IP Australia: Time 15:59 Date 2006-06-16
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| PCT/US2000/040459 WO2001010462A1 (en) | 1999-08-11 | 2000-07-25 | Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies |
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Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL200134B1 (en) | 1999-05-07 | 2008-12-31 | Genentech Inc | Treatment of autoimmunologic diseases with antagonists binding to cell surface markers |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| WO2004035607A2 (en) | 2002-10-17 | 2004-04-29 | Genmab A/S | Human monoclonal antibodies against cd20 |
| TWI335821B (en) | 2002-12-16 | 2011-01-11 | Genentech Inc | Immunoglobulin variants and uses thereof |
| KR20110044809A (en) | 2003-04-09 | 2011-04-29 | 제넨테크, 인크. | Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor |
| EP1626993B1 (en) | 2003-05-09 | 2015-03-11 | Duke University | Cd20-specific antibodies and methods of employing same |
| MXPA05013117A (en) | 2003-06-05 | 2006-03-17 | Genentech Inc | Combination therapy for b cell disorders. |
| ME03330B (en) | 2003-11-05 | 2019-10-20 | Roche Glycart Ag | Cd20 antibodies with increased fc receptor binding affinity and effector function |
| US7850962B2 (en) | 2004-04-20 | 2010-12-14 | Genmab A/S | Human monoclonal antibodies against CD20 |
| MY194883A (en) | 2004-06-04 | 2022-12-21 | Genentech Inc | Method for treating multiple sclerosis |
| EP2213683B1 (en) | 2004-08-04 | 2013-06-05 | Mentrik Biotech, LLC | Variant Fc regions |
| US10307481B2 (en) | 2005-07-25 | 2019-06-04 | Aptevo Research And Development Llc | CD37 immunotherapeutics and uses thereof |
| WO2007014238A2 (en) | 2005-07-25 | 2007-02-01 | Trubion Pharmaceuticals, Inc. | Single dose use of cd20-specific binding molecules |
| MY149159A (en) | 2005-11-15 | 2013-07-31 | Hoffmann La Roche | Method for treating joint damage |
| ES2618543T3 (en) | 2005-11-23 | 2017-06-21 | Genentech, Inc. | Methods and compositions related to B lymphocyte assays |
| EP3805269A1 (en) | 2006-06-12 | 2021-04-14 | Aptevo Research and Development LLC | Single-chain multivalent binding proteins with effector function |
| CN101932591B (en) | 2007-07-09 | 2018-02-16 | 健泰科生物技术公司 | Disulfide bond reduction is prevented during the recombinant production of polypeptide |
| EP2233149B1 (en) | 2007-10-16 | 2016-02-10 | ZymoGenetics, Inc. | Combination of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and anti-CD20 agents for treatment of autoimmune disease |
| US7914785B2 (en) | 2008-01-02 | 2011-03-29 | Bergen Teknologieverforing As | B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
| EP2077281A1 (en) | 2008-01-02 | 2009-07-08 | Bergen Teknologioverforing AS | Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
| WO2009126944A1 (en) | 2008-04-11 | 2009-10-15 | Trubion Pharmaceuticals, Inc. | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
| TW201438738A (en) | 2008-09-16 | 2014-10-16 | Genentech Inc | Methods for treating progressive multiple sclerosis |
| ES2468391T3 (en) * | 2008-12-22 | 2014-06-16 | Millennium Pharmaceuticals, Inc. | Combination of Aurora kinase inhibitors and anti-CD20 antibodies |
| WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
| JO3434B1 (en) | 2009-07-31 | 2019-10-20 | Millennium Pharm Inc | Pharmaceutical compositions for the treatment of cancer and other diseases or disorders |
| RU2639288C2 (en) | 2009-08-11 | 2017-12-20 | Дженентек, Инк. | Proteins production in cultural media without glutamine |
| MX341687B (en) | 2010-02-10 | 2016-08-30 | Immunogen Inc | Cd20 antibodies and uses thereof. |
| WO2011103089A1 (en) | 2010-02-19 | 2011-08-25 | Millennium Pharmaceuticals, Inc. | Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6--methoxyphenyl)-5h -pyrimido[5,4-d][2]benzazepin-2yl]amino}-2-methoxybenzoate |
| US9814740B2 (en) * | 2010-12-21 | 2017-11-14 | Duke University | Methods and compositions combining immunotherapy with monocyte activation |
| US10017739B2 (en) | 2012-09-06 | 2018-07-10 | Duke University | Methods of expanding and assessing B cells and using expanded B cells to treat disease |
| CN105209042B (en) | 2013-03-22 | 2019-03-08 | 米伦纽姆医药公司 | The combination of 1/2 inhibitor of catalytic MTORC and selective aurora A kinase inhibitor |
| CA2970738A1 (en) * | 2015-01-23 | 2016-07-28 | Immunomedics, Inc. | Combination therapy with anti-cd74 and anti-cd20 antibodies in patients with relapsed and refractory b-cell non-hodgkin's lymphoma |
| PL3303373T3 (en) | 2015-05-30 | 2020-09-21 | Molecular Templates, Inc. | De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
| MY193078A (en) | 2015-06-24 | 2022-09-26 | Hoffmann La Roche | Anti-transferrin receptor antibodies with tailored affinity |
| WO2017053469A2 (en) | 2015-09-21 | 2017-03-30 | Aptevo Research And Development Llc | Cd3 binding polypeptides |
| AR106189A1 (en) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | BIESPECTIFIC ANTIBODIES AGAINST HUMAN A-b AND THE HUMAN TRANSFERRINE RECEIVER AND METHODS OF USE |
| PE20181004A1 (en) | 2015-10-02 | 2018-06-26 | Hoffmann La Roche | BISPECIFIC ANTIBODIES AGAINST HUMAN CD20 AND THE HUMAN TRANSFERRIN RECEPTOR AND METHODS OF USE |
| CA3035268A1 (en) * | 2016-09-16 | 2018-03-22 | Nordic Nanovector Asa | Treatment of non-hodgkin lymphoma using lilotomab and 177lu-lilotomab satetraxetan |
| CN108421048B (en) * | 2016-09-28 | 2021-04-20 | 首都医科大学附属北京世纪坛医院 | Nano active carbon targeted drug delivery system, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5595721A (en) * | 1993-09-16 | 1997-01-21 | Coulter Pharmaceutical, Inc. | Radioimmunotherapy of lymphoma using anti-CD20 |
| US5843439A (en) * | 1992-11-13 | 1998-12-01 | Anderson; Darrell R. | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1689646A (en) * | 1998-08-11 | 2005-11-02 | 拜奥根Idec公司 | Combination therapies for B-cell lynphomas comprising administration of anti-CD20 antibody |
| US8557244B1 (en) * | 1999-08-11 | 2013-10-15 | Biogen Idec Inc. | Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody |
| US6451284B1 (en) * | 1999-08-11 | 2002-09-17 | Idec Pharmaceuticals Corporation | Clinical parameters for determining hematologic toxicity prior to radioimmunotheraphy |
-
2000
- 2000-07-25 CN CNB008116644A patent/CN100389825C/en not_active Expired - Lifetime
- 2000-07-25 CN CNA2008100921383A patent/CN101259270A/en active Pending
- 2000-07-25 CA CA002378646A patent/CA2378646A1/en not_active Abandoned
- 2000-07-25 EP EP00965561A patent/EP1207906A4/en not_active Withdrawn
- 2000-07-25 WO PCT/US2000/040459 patent/WO2001010462A1/en active Application Filing
- 2000-07-25 JP JP2001514978A patent/JP2003513012A/en active Pending
- 2000-07-25 MX MXPA02001398A patent/MXPA02001398A/en active IP Right Grant
- 2000-07-25 AU AU76260/00A patent/AU784971B2/en not_active Expired
- 2000-08-03 MY MYPI20003551A patent/MY136635A/en unknown
- 2000-08-10 TW TW089116114A patent/TWI279233B/en not_active IP Right Cessation
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2002
- 2002-02-08 NO NO20020639A patent/NO20020639L/en not_active Application Discontinuation
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2003
- 2003-02-18 HK HK03101198.5A patent/HK1048945A1/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843439A (en) * | 1992-11-13 | 1998-12-01 | Anderson; Darrell R. | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
| US5595721A (en) * | 1993-09-16 | 1997-01-21 | Coulter Pharmaceutical, Inc. | Radioimmunotherapy of lymphoma using anti-CD20 |
Non-Patent Citations (1)
| Title |
|---|
| MALONEY ET AL.MONOCHONAL ANTI.ONCOLOGY(1998)VOL12NO.8PP63-76 * |
Also Published As
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| HK1048945A1 (en) | 2003-04-25 |
| EP1207906A4 (en) | 2005-07-06 |
| NO20020639L (en) | 2002-04-11 |
| NO20020639D0 (en) | 2002-02-08 |
| CN1373671A (en) | 2002-10-09 |
| TWI279233B (en) | 2007-04-21 |
| CN100389825C (en) | 2008-05-28 |
| EP1207906A1 (en) | 2002-05-29 |
| MXPA02001398A (en) | 2002-08-12 |
| AU7626000A (en) | 2001-03-05 |
| JP2003513012A (en) | 2003-04-08 |
| CA2378646A1 (en) | 2001-02-15 |
| CN101259270A (en) | 2008-09-10 |
| WO2001010462A1 (en) | 2001-02-15 |
| MY136635A (en) | 2008-11-28 |
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| TC | Change of applicant's name (sec. 104) |
Owner name: BIOGEN IDEC INC. Free format text: FORMER NAME: IDEC PHARMACEUTICALS CORPORATION |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |