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1. Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial

Author

van de Loosdrecht, A. A., Cremers, E. M. P., Alhan, C., Duetz, C., in ’t Hout, F. E. M., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M., Ossenkoppele, G. J., Janssen, J. J. W. M., Klein, S. K., Vellenga, E., Huls, G. A., Muus, P., Langemeijer, S. M. C., de Greef, G. E., te Boekhorst, P. A. W., Raaijmakers, M. H. G., van Marwijk Kooy, M., Legdeur, M. C., Wegman, J. J., Deenik, W., de Weerdt, O., van Maanen-Lamme, T. M., Jobse, P., van Kampen, R. J. W., Beeker, A., Wijermans, P. W., Biemond, B. J., Tanis, B. C., van Esser, J. W. J., Schaar, C. G., Noordzij-Nooteboom, H. S., Jacobs, E. M. G., de Graaf, A. O., Jongen-Lavrencic, M., Stevens-Kroef, M. J. P. L., Westers, T. M., and Jansen, J. H.

Published
2024
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3. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome

Author

Janssen, J. J. W. M., Löwenberg, B., Manz, M., Biemond, B. J., Westerweel, P. E., Klein, S. K., Fehr, M., Sinnige, H. A. M., Efthymiou, A., Legdeur, M. C. J. C., Pabst, T., Gregor, M., van der Poel, M. W. M., Deeren, D., Tick, L. W., Jongen-Lavrencic, M., van Obbergh, F., Boersma, R. S., de Weerdt, O., Chalandon, Y., Heim, D., Spertini, O., van Sluis, G., Graux, C., Stüssi, G., van Norden, Y., and Ossenkoppele, G. J.

Published
2022
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4. Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes:the HOVON89 trial

Author

van de Loosdrecht, A. A., Cremers, E. M.P., Alhan, C., Duetz, C., in ’t Hout, F. E.M., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M., Ossenkoppele, G. J., Janssen, J. J.W.M., Klein, S. K., Vellenga, E., Huls, G. A., Muus, P., Langemeijer, S. M.C., de Greef, G. E., te Boekhorst, P. A.W., Raaijmakers, M. H.G., van Marwijk Kooy, M., Legdeur, M. C., Wegman, J. J., Deenik, W., de Weerdt, O., van Maanen-Lamme, T. M., Jobse, P., van Kampen, R. J.W., Beeker, A., Wijermans, P. W., Biemond, B. J., Tanis, B. C., van Esser, J. W.J., Schaar, C. G., Noordzij-Nooteboom, H. S., Jacobs, E. M.G., de Graaf, A. O., Jongen-Lavrencic, M., Stevens-Kroef, M. J.P.L., Westers, T. M., Jansen, J. H., van de Loosdrecht, A. A., Cremers, E. M.P., Alhan, C., Duetz, C., in ’t Hout, F. E.M., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M., Ossenkoppele, G. J., Janssen, J. J.W.M., Klein, S. K., Vellenga, E., Huls, G. A., Muus, P., Langemeijer, S. M.C., de Greef, G. E., te Boekhorst, P. A.W., Raaijmakers, M. H.G., van Marwijk Kooy, M., Legdeur, M. C., Wegman, J. J., Deenik, W., de Weerdt, O., van Maanen-Lamme, T. M., Jobse, P., van Kampen, R. J.W., Beeker, A., Wijermans, P. W., Biemond, B. J., Tanis, B. C., van Esser, J. W.J., Schaar, C. G., Noordzij-Nooteboom, H. S., Jacobs, E. M.G., de Graaf, A. O., Jongen-Lavrencic, M., Stevens-Kroef, M. J.P.L., Westers, T. M., and Jansen, J. H.

Abstract

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Published
2024

6. Leukemieën en myelodysplasie

Author

Ossenkoppele, G. J., Cornelissen, J. J., Sonneveld, P., van de Velde, C.J.H., editor, van der Graaf, W.T.A., editor, van Krieken, J.H.J.M., editor, and Marijnen, C.A.M., editor

Published
2017
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7. ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0

Author

Kiesewetter, B, Dafni, U, de Vries, EGE, Barriuso, J, Curigliano, G, González-Calle, V, Galotti, M, Gyawali, B, Huntly, BJP, Jäger, U, Latino, NJ, Malcovati, L, Oosting, SF, Ossenkoppele, G, Piccart, M, Raderer, M, Scarfò, L, Trapani, D, Zielinski, CC, Wester, R, Zygoura, P, Macintyre, E, Cherny, NI, ESMO-MCBS Working Group and Extended Working Group, Huntly, Brian [0000-0003-0312-161X], and Apollo - University of Cambridge Repository

Subjects
clinical trials, quality of life, clinical benefit, ESMO-MCBS, haematological malignancies, value frameworks
Abstract

BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.

Published
2023
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9. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry

Author

Hoffmann, V S, Baccarani, M, Hasford, J, Castagnetti, F, Di Raimondo, F, Casado, L F, Turkina, A, Zackova, D, Ossenkoppele, G, Zaritskey, A, Höglund, M, Simonsson, B, Indrak, K, Sninska, Z, Sacha, T, Clark, R, Bogdanovic, A, Hellmann, A, Griskevicius, L, Schubert-Fritschle, G, Sertic, D, Guilhot, J, Lejniece, S, Zupan, I, Burgstaller, S, Koskenvesa, P, Everaus, H, Costeas, P, Lindoerfer, D, Rosti, G, Saussele, S, Hochhaus, A, and Hehlmann, R

Published
2017
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10. Correction: Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, M. C., van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., and Löwenberg, B.

Published
2020
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12. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Published
2017
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16. In-Vitro Cellular Drug Resistance in Acute Non-Lymhoblastic Leukemia: Comparisons Between Adults and Children

Author

De Haas, T. G. K. J., Zwaan, Ch. M., Wondergem, M. J., Pieters, R., Kaspers, G. J. L., Loonen, A. H., Rottier, M. M. A., WüNsche, R., Creutzig, U., Bartl, S., HäHlen, K., Broxterman, Hj., Ossenkoppele, G. J., Veerman, A. J. R., Büchner, T., editor, Hiddemann, W., editor, Wörmann, B., editor, Schellong, G., editor, Ritter, J., editor, and Creutzig, U., editor

Published
2001
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21. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years

Author

Cornelissen, J J, Versluis, J, Passweg, J R, van Putten, W L J, Manz, M G, Maertens, J, Beverloo, H B, Valk, P J M, van Marwijk Kooy, M, Wijermans, P W, Schaafsma, M R, Biemond, B J, Vekemans, M-C, Breems, D A, Verdonck, L F, Fey, M F, Jongen-Lavrencic, M, Janssen, J J W M, Huls, G, Kuball, J, Pabst, T, Graux, C, Schouten, H C, Gratwohl, A, Vellenga, E, Ossenkoppele, G, and Löwenberg, B

Published
2015
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22. S130: NPM1 MUTATED AML: IMPACT OF CO-MUTATIONAL PATTERNS - RESULTS OF THE EUROPEAN HARMONY ALLIANCE

Author

Hernández-Sánchez, A., primary, Villaverde-Ramiro, Á., additional, Martínez Elicegui, J., additional, González, T., additional, Benner, A., additional, Sträng, E., additional, Castellani, G., additional, Heckman, C. A., additional, Versluis, J., additional, Abáigar, M., additional, Sobas, M., additional, Azibeiro, R., additional, Tur, L., additional, Valk, P. J., additional, Metzeler, K. H., additional, Ayala, R., additional, Dall’Olio, D., additional, Tettero, J., additional, Martínez-López, J., additional, Dombret, H., additional, Pratcorona, M., additional, Damm, F., additional, Mills, K. I., additional, Mayer, J., additional, Thiede, C., additional, Voso, M. T., additional, Sanz, G. F., additional, Calado, F., additional, Döhner, K., additional, Gaidzik, V. I., additional, Heuser, M., additional, Haferlach, T., additional, Turki, A. T., additional, Reinhardt, D., additional, Villoria Medina, R., additional, van Speybroeck, M., additional, Schulze-Rath, R., additional, Barbus, M., additional, Butler, J. E., additional, Hernández Rivas, J. M., additional, Huntly, B. J., additional, Ossenkoppele, G. J., additional, Döhner, H., additional, and Bullinger, L., additional

Published
2022
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23. P406: ENHANCED SIGNIFICANCE OF FLT3-ITD RESIDUAL DISEASE DETECTION ON TREATMENT OUTCOME IN ACUTE MYELOID LEUKEMIA

Author

Grob, T., primary, Sanders, M., additional, Vonk, C., additional, Kavelaars, F., additional, Rijken, M., additional, Hanekamp, D., additional, Gradowska, P., additional, Cloos, J., additional, Fløisand, Y., additional, Marwijk Kooy, M. V., additional, Manz, M., additional, Ossenkoppele, G., additional, Tick, L., additional, Havelange, V., additional, Löwenberg, B., additional, Jongen-Lavrencic, M., additional, and Valk, P., additional

Published
2022
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24. Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status

Author

Roboz, GJ, Ravandi, F, Wei, AH, Dombret, H, Thol, F, Voso, MT, Schuh, AC, Porkka, K, La Torre, I, Skikne, B, Zhong, J, Beach, CL, Risueno, A, Menezes, DL, Ossenkoppele, G, Dohner, H, Roboz, GJ, Ravandi, F, Wei, AH, Dombret, H, Thol, F, Voso, MT, Schuh, AC, Porkka, K, La Torre, I, Skikne, B, Zhong, J, Beach, CL, Risueno, A, Menezes, DL, Ossenkoppele, G, and Dohner, H

Abstract

Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD- status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD- during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.

Published
2022

25. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Janssen, J J W M, Löwenberg, B, Manz, M, Biemond, B J, Westerweel, P E, Klein, S K, Fehr, M, Sinnige, H A M, Efthymiou, A, Legdeur, M C J C, Pabst, T, Gregor, M, van der Poel, M W M, Deeren, D, Tick, L W, Jongen-Lavrencic, M, van Obbergh, F, Boersma, R S, de Weerdt, O, Chalandon, Y, Heim, D, Spertini, O, van Sluis, G, Graux, Carlos, Stüssi, G, van Norden, Y, Ossenkoppele, G J, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Janssen, J J W M, Löwenberg, B, Manz, M, Biemond, B J, Westerweel, P E, Klein, S K, Fehr, M, Sinnige, H A M, Efthymiou, A, Legdeur, M C J C, Pabst, T, Gregor, M, van der Poel, M W M, Deeren, D, Tick, L W, Jongen-Lavrencic, M, van Obbergh, F, Boersma, R S, de Weerdt, O, Chalandon, Y, Heim, D, Spertini, O, van Sluis, G, Graux, Carlos, Stüssi, G, van Norden, Y, and Ossenkoppele, G J

Abstract

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Published
2022

30. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study

Author

Hochhaus, A, Rosti, G, Cross, N CP, Steegmann, J L, le Coutre, P, Ossenkoppele, G, Petrov, L, Masszi, T, Hellmann, A, Griskevicius, L, Wiktor-Jedrzejczak, W, Rea, D, Coriu, D, Brümmendorf, T H, Porkka, K, Saglio, G, Gastl, G, Müller, M C, Schuld, P, Di Matteo, P, Pellegrino, A, Dezzani, L, Mahon, F-X, Baccarani, M, and Giles, F J

Published
2016
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36. EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

Author

Kiesewetter, B., Cherny, N. I., Boissel, Nicolas, Cerisoli, F., Dafni, U., De Vries, Elisabeth G. E., Ghia, Paolo, Gökbuget, N., González-Calle, Verónica, Huntly, B., Jäger, U., Latino, N. J., Douillard, Jean-Yves, Malcovati, L., Mateos, M. V., Ossenkoppele, G. J., Porkka, K., Raderer, M., Ribera, Jose-Maria, Scarfò, L., Wester, R., Zygoura, P., Sonneveld, P., Universitat Autònoma de Barcelona, Hematology, Radiotherapy, CCA - Cancer Treatment and quality of life, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Kiesewetter, Barbara [0000-0002-5490-2371], Apollo - University of Cambridge Repository, Kiesewetter, B., Cherny, N. I., Boissel, N., Cerisoli, F., Dafni, U., De Vries, E. G. E., Ghia, P., Gokbuget, N., Gonzalez-Calle, V., Huntly, B., Jager, U., Latino, N. J., Douillard, J. -Y., Malcovati, L., Mateos, M. -V., Ossenkoppele, G. J., Porkka, K., Raderer, M., Ribera, J. -M., Scarfo', L., Wester, R., Zygoura, P., Sonneveld, P., HUS Comprehensive Cancer Center, Hematologian yksikkö, and Helsinki University Hospital Area

Subjects
Cancer Research, medicine.medical_specialty, 3122 Cancers, value frameworks, ESMO-MCBS, Haematologic malignancies, Chronic lymphatic leukemia, Clinical benefit, 03 medical and health sciences, 0302 clinical medicine, QUALITY-OF-LIFE, Rating scale, Chronic leukaemia, REFRACTORY MULTIPLE-MYELOMA, Outcome Assessment, Health Care, medicine, Hematologic malignancy, Humans, ddc:610, Intensive care medicine, Grading (tumors), Societies, Medical, Original Research, 030304 developmental biology, RISK MYELODYSPLASTIC SYNDROMES, Solid tumour, 0303 health sciences, haematologic malignancies, business.industry, CHRONIC LYMPHOCYTIC-LEUKEMIA, Value frameworks, Myelodysplastic syndromes, clinical benefit, STEM-CELL TRANSPLANTATION, medicine.disease, LITY-OF-LIFE, 3. Good health, Clinical trial, LOW-DOSE CYTARABINE, Oncology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, BORTEZOMIB-MELPHALAN-PREDNISONE, TRANSFUSION-DEPENDENT PATIENTS, OBINUTUZUMAB PLUS BENDAMUSTINE, business, NON-HODGKIN-LYMPHOMA
Abstract

OBJECTIVE: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).METHODS: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies.RESULTS: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described.CONCLUSIONS: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials.

Published
2020
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37. HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) INDUCES DURABLE REMISSIONS IN PATIENTS WITH POEMS SYNDROME: A RETROSPECTIVE STUDY OF THE PLASMA CELL DISORDERS SUBCOMMITTEE OF THE CHRONIC MALIGNANCY WORKING PARTY OF THE EBMT: PH-O134

Author

Cook, G., Garderet, L., Iacobelli, S., van Biezen, A., Hoek, J., Rovira, M., Byrne, J., Bordessoule, D., Leone, G., Nagler, A., Castagna, L., Cook, M., Legros, L., Ossenkoppele, G., Leblond, V., Morris, T., and Kroger, N.

Published
2014

42. Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting

Author

Lang, K.M., Harrison, K.L., Williamson, P.R., Huntly, B.J.P., Ossenkoppele, G., Geissler, J., Bereczky, T., Hernández-Rivas, J.M., Chevrou-Séverac, H., Goodbody, R., Schulze-Rath, R., and Bullinger, L.

Subjects
Cancer Research
Abstract

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has an unacceptably low cure rate. In recent years, a number of new treatment strategies and compounds were developed for the treatment of AML. There were several randomized controlled clinical trials with the objective to improve patients' management and patients' outcome in AML. Unfortunately, these trials are not always directly comparable since they do not measure the same outcomes, and currently there are no core outcome sets that can be used to guide outcome selection and harmonization in this disease area. The HARMONY (Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology) Alliance is a public-private European network established in 2017 and currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. Accordingly, this pilot study will be performed to define a core outcome set in AML. METHODS: The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations. At the pre-Delphi stage, a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently, the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completion of the last Delphi round, a final face-to-face meeting is planned to achieve consensus about the core outcome set in AML. DISCUSSION: As part of the HARMONY Alliance, the pilot Delphi aims to define a core outcome set in AML on the basis of a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real-world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.

Published
2020

43. Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Author

Janssen, J, Löwenberg, Bob, Manz, M, Bargetzi, M, Biemond, B, van den Borne, P, Breems, D, Brouwer, R, Chalandon, Y, Deeren, D, Efthymiou, A, Gjertsen, BT, Graux, C, Gregor, M, Heim, D, Hess, U, Hoogendoorn, M, Jaspers, A, Jie, A, Jongen - Lavrencic, Mojca, Klein, S, van der Klift, Maarten, Kuball, J, van Lammeren-Venema, D, Legdeur, MC, van de Loosdrecht, A, Maertens, J, Kooy, MM, Moors, I, Nijziel, M, van Obbergh, F, Oosterveld, M, Pabst, T, Poel, M, Sinnige, H, Spertini, O, Terpstra, W, Tick, L, van der Velden, W, Vekemans, MC, Vellenga, E, de Weerdt, O, Westerweel, P, Stüssi, G, van Norden, Yvette, Ossenkoppele, G, Janssen, J, Löwenberg, Bob, Manz, M, Bargetzi, M, Biemond, B, van den Borne, P, Breems, D, Brouwer, R, Chalandon, Y, Deeren, D, Efthymiou, A, Gjertsen, BT, Graux, C, Gregor, M, Heim, D, Hess, U, Hoogendoorn, M, Jaspers, A, Jie, A, Jongen - Lavrencic, Mojca, Klein, S, van der Klift, Maarten, Kuball, J, van Lammeren-Venema, D, Legdeur, MC, van de Loosdrecht, A, Maertens, J, Kooy, MM, Moors, I, Nijziel, M, van Obbergh, F, Oosterveld, M, Pabst, T, Poel, M, Sinnige, H, Spertini, O, Terpstra, W, Tick, L, van der Velden, W, Vekemans, MC, Vellenga, E, de Weerdt, O, Westerweel, P, Stüssi, G, van Norden, Yvette, and Ossenkoppele, G

Abstract

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.

Published
2021

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