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  • 1
    Online Resource
    Online Resource
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 4817-4817
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4817-4817
    Abstract: Introduction: Bendamustine (BEN) provides effective treatment of hematologic as well as of non-hematologic malignancies. It is characterized by an unique activity profile which differs from common nitrogen mustard drugs. In particular, it causes only partial cross resistance to other alkylating agents, anthracyclines and anti-metabolites, respectively. BEN is used in patients with chemo naïve, relapsed or refractory chronic lymphocytic leukemia (CLL), however, no head-to-head study has been performed so far. Therefore, a multicenter, international phase III study was initiated to compare the activity of BEN against chlorambucil in treatment-naive B-CLL patients with Binet stage B/C. Patients and Methods: Patients are randomized to either Arm A (BEN 100 mg/m2, d 1+2) or to Arm B (chlorambucil 0,8mg/kg Broca’s weight, d 1+15) to receive a maximum of 6 treatment cycles. Primary objectives are overall remission rate and progression-free survival. The anticipated effects are an overall remission rate of 60% vs. 30% and a median progression free survival of 20 vs.14 months. Secondary objectives are additional efficacy parameters, safety, and quality of life. The study design is adaptive with four interim analyses to adjust the final number of patients, plus one safety analysis. A maximum of 350 patients is planned. Toxicities regarding hemoglobin, platelets and neutrophils are graded according to the NCIWG for CLL, while leukocyte and lymphocyte counts are graded according to CTC as in many other CLL trials. Results and Summary: To assess safety, twenty patients in each treatment arm with at least one completed treatment cycle have been evaluated. The results have been reviewed by an independent data monitoring committee (IDMC). It was concluded that the dosages selected for both treatment arms are safe and that the study is to be continued. Furthermore, another safety analysis was performed with respect to the rate of major infections in the same patient cohort after having completed study treatment. While the infection rate has been reported to be 29% in patients treated with fludarabine as published by Rai et al., in our study two BEN-patients (10%) experienced major infections whereas none occurred in the chlorambucil arm. One BEN-patient developed fever CTC grade 3 without neutropenia. Another patient experienced pneumonia CTC grade 2 requiring hospitalization and intravenous antibiotic treatment. In the BEN-arm, 87% of the scheduled dose was applied whereas 89% was given in the chlorambucil arm. Patients treated with BEN remained longer on study as compared to the chlorambucil patients. The toxicity rate, both hematologic and non-hematologic, was in favour for chlorambucil. In total, three patients were withdrawn from study due to toxicity: one patient in each treatment arm due to infection and one BEN-patient due to an allergic reaction. Meanwhile, the first planned interim analysis on remission rate was done. 43 patients in each treatment arm were evaluated. The IDMC recommended to continue the study. A second interim analysis will be performed after 160 patients will have completed the first tumor evaluation to adjust the number of patients finally required.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 45, No. 12 ( 2004-12-01), p. 2455-2458
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2004
    detail.hit.zdb_id: 2030637-4
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  • 3
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 880-880
    Abstract: Treatment of elderly patients (pts) with AML requires a sensitive balance between efficacy and toxicity. In the AML97 study all pts with AML 〉 60 years (y) were registered and, according to their clinical status, treated in curative, palliative or supportive intention. From a total of 520 pts enrolled, 375 (72%) pts were allocated to the curative, 112 (22%) to the palliative and 33 (6%) to the supportive part of the protocol. Patient characteristics between the 3 groups differed in respect to age, but not in regard to the distribution de novo and secondary AML. Median age of the pts was 66 y (range 60–80 y), 75 y (range 64–90 y) and 76 y (range 63–97 y) for the curative, palliative and supportive protocol respectively. Curative treatment consisted of one (in case of PR after the first chemotherapy of two) courses of induction therapy (AraC 2 g/m2 iv on day (d) 1,3,5,7 in combination with mitoxantrone 10 mg/m2 iv d 1-3) followed by two consolidation courses (AraC 240 mg/m2 iv d 1-5 combined with mitoxantrone 10 mg/m2 iv d 1-2). Palliative treatment included idarubicin 10 mg po d 1 in combination with thioguanine 40 mg po d 1-5, or AraC 80 mg sc d 1-5 or etoposide 100mg po d 1-5. In the supportive arm transfusions were applied. CR was obtained in 75% (95 CI: 68–82%) of pts with de novo AML and in 61% (95 CI: 50–70%) of pts with secondary AML in the curative arm with an early death rate of 12 % (95CI: 7–17%) and 19% (95 CI: 12–24%) respectively. Cytogenetic risk factors at diagnosis were the most important prognostic factor for CR (p 〈 0,0005, multivariate analysis). Pts with favourable karyotype achieved CR in 93%, with normal in 80 %, with other aberrations in 79% and with unfavourable karyotype in 46%. The overall survival (OS) after 2 years in the curative part of protocol was 0,31 ± 0,03 for all pts. With a median follow up of 283 d (range 33 – 1688) the actual OS was 0,58 ± 0,15, 0,38 ± 0,06, 0,39 ± 0,09 and 0,14 ± 0,05 for pts with favourable, normal, other and unfavourable cytogenetics respectively. Interestingly age was not an important determinant, even if results were analysed in a cohort of 603 pts with AML of any age with a similar induction therapy. CR rates of pts below and above 60 y were identical, if they were stratified by cytogenetic risk factors. Median survival was 54 d and only 12 d for pts treated with palliative chemotherapy and supportive therapy respectively. We conclude, that the curative protocol is able to induce high CR in pts with AML 〉 60 y with low mortality and CR are not different to those of pts 〈 60 y, if cytogenetics are taking into account. Despite high CR rate, OS remains low and consolidation therapy need to be improved. Transplant protocols with reduced intensity conditioning are currently tested in these patients. Treatment results in the palliative arm are disappointing and confirm the need to develop novel therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2002
    In:  Biologie in unserer Zeit Vol. 32, No. 5 ( 2002-9), p. 304-310
    In: Biologie in unserer Zeit, Wiley, Vol. 32, No. 5 ( 2002-9), p. 304-310
    Type of Medium: Online Resource
    ISSN: 0045-205X , 1521-415X
    RVK:
    Language: Unknown
    Publisher: Wiley
    Publication Date: 2002
    detail.hit.zdb_id: 120079-3
    detail.hit.zdb_id: 2006653-3
    SSG: 12
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  • 5
    In: Blood, American Society of Hematology, Vol. 103, No. 2 ( 2004-01-15), p. 725-731
    Abstract: New conditioning regimens are being explored to reduce toxicity and enable allogeneic bone marrow transplantation in patients not eligible for conventional transplantation. We have investigated treosulfan, an alkylating agent, with the aim of developing an efficient and reliable but less-toxic conditioning regimen. A series of 30 patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (n = 14) or unrelated (n = 16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenously daily for 5 days. Patients receiving grafts from unrelated donors also were given rabbit antithymocyte globulin 10 mg/kg intravenously daily for 3 days. All patients achieved prompt neutrophil and platelet recovery. Extramedullary toxicity was generally mild with Common Toxicity Criteria (CTC) grade 3 or 4 attributable to the conditioning seen only with transaminases. Complete donor chimerism was achieved by 90% of the patients. Acute graft-versus-host disease (GVHD) grade III or IV developed in 14% of the patients and chronic GVHD in 39%. An estimated overall survival rate of 73% and an event-free survival rate of 49% have been reached after a median of 22 months (range, 7.4-33.4 months). In summary, the combination of treosulfan and fludarabine is a safe and efficient conditioning regimen.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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