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Farhad Ravandi - One of the best experts on this subject based on the ideXlab platform.
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Idarubicin cytarabine and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high risk myelodysplastic syndrome a single arm phase 2 study
The Lancet Haematology, 2019Co-Authors: Farhad Ravandi, Rita Assi, Naval Daver, Tapan M Kadia, Gautam Borthakur, Christopher B Benton, Philip A Thompson, Yesid AlvaradoAbstract:Summary Background Outcomes for younger patients with acute myeloid leukaemia have moderately improved over the past two decades owing to better supportive care and recent introduction of novel targeted agents. Blocking PD-1 and its ligand's pathways enhances antileukaemia responses by enabling T cells in murine models. We aimed to assess the addition of nivolumab to frontline therapy with Idarubicin and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome. Methods This single-arm, phase 2 part of the phase 1–2 study of nivolumab in combination with Idarubicin and cytarabine was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 18–60 years (or >60 years if suitable for intensive chemotherapy), and had newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome, and an Eastern Cooperative Oncology Group performance status of 0–2. Induction included cytarabine 1·5 g/m2 by 24-h continuous infusion daily on days 1–4 (3 days in patients >60 years) and Idarubicin 12 mg/m2 daily on days 1–3. Nivolumab 3 mg/kg was started on day 24 (range 22–26) and continued every 2 weeks for up to a year in responders. Responders received either up to five consolidation cycles of attenuated doses of Idarubicin and cytarabine, or allogeneic stem cell transplantation if eligible. The primary endpoint was event-free survival. Efficacy and safety analyses were done in all patients who received at least one dose of study treatment. Secondary endpoints were relapse-free survival and overall survival. This ongoing trial is registered with ClinicalTrials.gov , number NCT02464657 . Findings Between Aug 7, 2015, and June 2, 2018, 44 patients were enrolled of whom 22 (50%) had adverse genetic risk by European Leukaemia Network classification. All patients were evaluable for safety and efficacy. At a median follow-up of 17·25 months (IQR 0·50–30·40), median event-free survival was not reached (95% CI 7·93–NR). Median relapse-free survival of responders was 18·54 months (95% CI 8·20–23·22). The median overall survival was 18·54 months (95% CI 10·81–28·81). Six patients had seven grade 3–4 immune-related adverse events with two cases of rash, two of colitis, and one each of transaminitis, pancreatitis, and cholecystitis. 19 (43%) of 44 patients achieved a response and proceeded to allogeneic stem cell transplantation, with grade 3–4 graft-versus-host disease observed in five (26%). No treatment related deaths were attributed to nivolumab. Interpretation Addition of nivolumab to induction chemotherapy with Idarubicin and cytarabine is feasible in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome. Post-transplant severe graft-versus-host disease could be improved, and earlier initiation of checkpoint inhibitor therapy is warranted in future studies. Funding The MD Anderson Cancer Center Support Grant CA016672 , and the MD Anderson Cancer Center Leukaemia SPORE CA100632 from the National Cancer Institute, Bristol Myers Squibb.
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a randomized phase 2 study of Idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia
Cancer, 2017Co-Authors: Elias Jabbour, Nicholas J Short, Lianchun Xiao, Varsha Gandhi, Guillermo Garciamanero, William Plunkett, Farhad Ravandi, Koji Sasaki, Xuelin Huang, Naveen PemmarajuAbstract:BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of Idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with Idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received Idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with Idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society.
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a randomized phase 2 study of Idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia
Cancer, 2017Co-Authors: Elias Jabbour, Nicholas J Short, Lianchun Xiao, Varsha Gandhi, Guillermo Garciamanero, William Plunkett, Farhad Ravandi, Koji Sasaki, Xuelin Huang, Naveen PemmarajuAbstract:BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of Idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with Idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received Idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with Idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society.
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longer follow up of the combination of clofarabine Idarubicin and cytarabine cia as frontline therapy for patients younger than 61 years with newly diagnosed acute myeloid leukemia aml
Blood, 2013Co-Authors: Aziz Nazha, Huang Xuelin, Sangbum Choi, Tapan M Kadia, Guillermo Garciamanero, Farhad Ravandi, Elias Jabbour, Marina KonoplevaAbstract:Background Clofarabine is a second generation nucleoside analogue with activity in adults with AML. In a phase II trial of clofarabine in combination with Idarubicin and cytarabine in newly diagnosed patients (pts) with acute myeloid leukemia (AML) Idarubicin and cyarabine (IA), the overall survival (OS) and event-free survival (EFS) were significantly longer for CIA treated pts and mainly for pts Idarubicin 6 mg/m2 daily (days 1-3), and Cytarabine 0.75 g/m2 daily (days 1-5). From pt 31 onward, induction doses were amended to Clofarabine 20 mg/m2 x 5, Idarubicin 10 mg/m2 x 3, and Cytarabine 1 g/m2 x 5. Pts who did not achieve a complete remission (CR) following induction could receive one re-induction course. Pts in CR/CRp continued with up to 6 consolidation cycles with Clofarabine 22.5 mg/m2 x 3, Idarubicin 6 mg/m2 X 2, and Cytarabine 0.75 g/m2 x 3, subsequently amended to Clofarabine 15 mg/m2 x 3, Idarubicin 8 mg/m2 x 2, and Cytarabine 0.75 g/m2x 3. Results From April 2010 until February 2012, 57 pts were evaluable. With median follow up of 21.5 months (1.5-33.4), the median OS was 27.4 months, median relapse-free survival was not reached, and median EFS was 11.5 months. Patients 40 years. Compared to a historical cohort of pts treated with IA, CIA continued to show superior OS (HR 0.8, CI 0.51-1.27, P = 0.043). In multivariate analysis, CIA retained its prognostic value on OS even when transplant was added as time dependent covariate (HR 0.84, CI 0.53-1.33, P = 0.04). Pts Research Funding. Ravandi: Sanofi-Aventis: Research Funding. Faderl: Sanofi-Aventis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.
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clofarabine Idarubicin and cytarabine cia as frontline therapy for patients 60 years with newly diagnosed acute myeloid leukemia
American Journal of Hematology, 2013Co-Authors: Aziz Nazha, Sangbum Choi, Tapan M Kadia, Guillermo Garciamanero, Farhad Ravandi, Gautam Borthakur, Elias Jabbour, Xuelin Huang, Marina KonoplevaAbstract:Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, Idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ≤60 years. Patients ≥18–60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m−2 IV daily (days 1–5), Idarubicin (I) 10 mg m−2 IV daily (days 1–3), and cytarabine (A) 1 g m−2 IV daily (days 1–5). Patients in remission received up to six consolidation cycles (C 15 mg m−2 × 3, I 8 mg m−2 × 2, and A 0.75 g m−2 × 3). Fifty-seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event-free survival (EFS) was 13.5 months. Most toxicities were ≤grade 2. Four week mortality was 2%. In subgroup analysis, patients ≤40 years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years. Compared to historical patients treated with Idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ≤60 years with newly diagnosed AML. Am. J. Heamtol. 88:961–966, 2013. © 2013 Wiley Periodicals, Inc.
Guillermo Garciamanero - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase 2 study of Idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia
Cancer, 2017Co-Authors: Elias Jabbour, Nicholas J Short, Lianchun Xiao, Varsha Gandhi, Guillermo Garciamanero, William Plunkett, Farhad Ravandi, Koji Sasaki, Xuelin Huang, Naveen PemmarajuAbstract:BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of Idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with Idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received Idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with Idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society.
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a randomized phase 2 study of Idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia
Cancer, 2017Co-Authors: Elias Jabbour, Nicholas J Short, Lianchun Xiao, Varsha Gandhi, Guillermo Garciamanero, William Plunkett, Farhad Ravandi, Koji Sasaki, Xuelin Huang, Naveen PemmarajuAbstract:BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of Idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with Idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received Idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with Idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society.
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longer follow up of the combination of clofarabine Idarubicin and cytarabine cia as frontline therapy for patients younger than 61 years with newly diagnosed acute myeloid leukemia aml
Blood, 2013Co-Authors: Aziz Nazha, Huang Xuelin, Sangbum Choi, Tapan M Kadia, Guillermo Garciamanero, Farhad Ravandi, Elias Jabbour, Marina KonoplevaAbstract:Background Clofarabine is a second generation nucleoside analogue with activity in adults with AML. In a phase II trial of clofarabine in combination with Idarubicin and cytarabine in newly diagnosed patients (pts) with acute myeloid leukemia (AML) Idarubicin and cyarabine (IA), the overall survival (OS) and event-free survival (EFS) were significantly longer for CIA treated pts and mainly for pts Idarubicin 6 mg/m2 daily (days 1-3), and Cytarabine 0.75 g/m2 daily (days 1-5). From pt 31 onward, induction doses were amended to Clofarabine 20 mg/m2 x 5, Idarubicin 10 mg/m2 x 3, and Cytarabine 1 g/m2 x 5. Pts who did not achieve a complete remission (CR) following induction could receive one re-induction course. Pts in CR/CRp continued with up to 6 consolidation cycles with Clofarabine 22.5 mg/m2 x 3, Idarubicin 6 mg/m2 X 2, and Cytarabine 0.75 g/m2 x 3, subsequently amended to Clofarabine 15 mg/m2 x 3, Idarubicin 8 mg/m2 x 2, and Cytarabine 0.75 g/m2x 3. Results From April 2010 until February 2012, 57 pts were evaluable. With median follow up of 21.5 months (1.5-33.4), the median OS was 27.4 months, median relapse-free survival was not reached, and median EFS was 11.5 months. Patients 40 years. Compared to a historical cohort of pts treated with IA, CIA continued to show superior OS (HR 0.8, CI 0.51-1.27, P = 0.043). In multivariate analysis, CIA retained its prognostic value on OS even when transplant was added as time dependent covariate (HR 0.84, CI 0.53-1.33, P = 0.04). Pts Research Funding. Ravandi: Sanofi-Aventis: Research Funding. Faderl: Sanofi-Aventis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.
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clofarabine Idarubicin and cytarabine cia as frontline therapy for patients 60 years with newly diagnosed acute myeloid leukemia
American Journal of Hematology, 2013Co-Authors: Aziz Nazha, Sangbum Choi, Tapan M Kadia, Guillermo Garciamanero, Farhad Ravandi, Gautam Borthakur, Elias Jabbour, Xuelin Huang, Marina KonoplevaAbstract:Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, Idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ≤60 years. Patients ≥18–60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m−2 IV daily (days 1–5), Idarubicin (I) 10 mg m−2 IV daily (days 1–3), and cytarabine (A) 1 g m−2 IV daily (days 1–5). Patients in remission received up to six consolidation cycles (C 15 mg m−2 × 3, I 8 mg m−2 × 2, and A 0.75 g m−2 × 3). Fifty-seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event-free survival (EFS) was 13.5 months. Most toxicities were ≤grade 2. Four week mortality was 2%. In subgroup analysis, patients ≤40 years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years. Compared to historical patients treated with Idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ≤60 years with newly diagnosed AML. Am. J. Heamtol. 88:961–966, 2013. © 2013 Wiley Periodicals, Inc.
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clofarabine Idarubicin and cytarabine cia as frontline therapy for patients 60 years with newly diagnosed acute myeloid leukemia aml
Blood, 2011Co-Authors: Aziz Nazha, Sangbum Choi, Tapan M Kadia, Guillermo Garciamanero, Farhad Ravandi, Gautam Borthakur, Elias Jabbour, Xuelin Huang, Marina KonoplevaAbstract:Abstract 1550 Background: Clofarabine is a second generation nucleoside analogue with activity in adults with AML. A recent randomized phase III study in AML relapse showed higher response rates and better event-free survival with the combination of clofarabine and cytarabine (CA) compared to cytarabine alone. We have also reported the feasibility and safety of the addition of Idarubicin to CA (CIA) in a previous phase I and II study. To explore this combination further, we conducted a phase II study of CIA in pts Patients and Methods: Patients (Pts) were eligible if they were 2, cardiac ejection fraction 2 iv daily (days 1–5), Idarubicin 6 mg/m 2 daily (days 1–3), and Cytarabine 0.75 g/m 2 daily (days 1–5). From pt 31 onward, induction doses were amended to Clofarabine 20 mg/m 2 × 5, Idarubicin 10 mg/m 2 × 3, and Cytarabine 1 g/m 2 × 5. Pts who have not achieved a complete remission following the induction could receive one re-induction course. Pts in CR or CRp continued with up to 6 consolidation cycles with Clofarabine 22.5 mg/m 2 × 3, Idarubicin 6 mg/m 2 (days 1–2), and Cytarabine 0.75 g/m 2 × 3, subsequently amended to Clofarabine 15 mg/m 2 × 3, Idarubicin 8 mg/m 2 × 2, and Cytarabine 0.75 g/m 2 × 3. Supportive care was standard. Pts ≥ 50 yrs were admitted to a laminar air flow room for the duration of the induction. Results: From April 2010 until August 2011, 51 pts have been accrued with a median age of 49 yrs (range 19–59): 33 pts (65%) with de novo AML and 18 pts (35%) with secondary AML (18 related to MDS, 7 related to therapy). Three pts (5%) had a PS of 2. Median WBC at diagnosis was 3.4 × 10 9 /L (0.6-92.3). Thirty-three (65%) pts had abnormal cytogenetics (21/33[64%] poor risk and 5/33 [15%] intermediate risk). Molecular profile: 6 pts (11%) had FLT3/ITD, 3 pts (6%) CEBPA, and 8 pts (16%) NPM1 mutations. Thirty-five pts (69%) achieved CR and 1 (2%) CRp for an overall response rate (ORR) of 71%. 61% pts (31/51) achieved CR following one induction cycle. 18% (9/51) pts required a re-induction and 44% (4/9) of them responded after the re-induction. Responding pts received a median of 2 courses (1–8) courses. With a median follow-up of 23 weeks (3–36+) median remission duration has not been reached with a 1-yr remission probability of 85%. Ten pts (19%) died on study including 2 (4%) who died grade 2 included elevated bilirubin (4%), hypokalemia (4%), cellulitis (4%) and seizure (1%). Myelosuppression was ubiquitous but prolonged myelosuppression > 42 days was infrequent. 76 % (39/51) pts had neutropenic fever. Conclusion: Clofarabine, Idarubicin and Cytarabine achieve a response rate of 71% in patients Disclosures: Off Label Use: Clofarabine, use of Clofarabine in AML. Ravandi: Genzyme: Research Funding. Kantarjian: Genzyme: Research Funding. Faderl: Genzyme: Membership on an entity9s Board of Directors or advisory committees, Research Funding.
J Ritter - One of the best experts on this subject based on the ideXlab platform.
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improved treatment results in high risk pediatric acute myeloid leukemia patients after intensification with high dose cytarabine and mitoxantrone results of study acute myeloid leukemia berlin frankfurt munster 93
Journal of Clinical Oncology, 2001Co-Authors: U Creutzig, J. Hermann, J Ritter, M. Zimmermann, Dirk Reinhardt, Frank Berthold, G Henze, H Jurgens, H Kabisch, W HaversAbstract:PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v Idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Munster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Esti...
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improved treatment results in high risk pediatric acute myeloid leukemia patients after intensification with high dose cytarabine and mitoxantrone results of study acute myeloid leukemia berlin frankfurt munster 93
Journal of Clinical Oncology, 2001Co-Authors: U Creutzig, J. Hermann, J Ritter, M. Zimmermann, Dirk Reinhardt, Frank Berthold, G Henze, H Jurgens, H Kabisch, W HaversAbstract:PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v Idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Munster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Esti...
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Idarubicin improves blast cell clearance during induction therapy in children with aml results of study aml bfm 93
Leukemia, 2001Co-Authors: J Ritter, Blutters D Sawatzki, J. Hermann, Charlotte M. Niemeyer, Benny Selle, M. Zimmermann, Helmut Gadner, Daniel Schwabe, Joachim BoosAbstract:Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93
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Idarubicin improves blast cell clearance during induction therapy in children with aml results of study aml bfm 93
Leukemia, 2001Co-Authors: J Ritter, Blutters D Sawatzki, J. Hermann, Charlotte M. Niemeyer, Benny Selle, M. Zimmermann, Helmut Gadner, Daniel Schwabe, Joachim BoosAbstract:In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day Idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the Idarubicin arm (25 of 144 = 17% of patients with ⩾5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pχ2 = 0.01). This was, however, mainly seen in high risk patients treated with Idarubicin (19% vs 38%, Pχ2 = 0.007). Cardiotoxicity, WHO grade 1–3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/μl of 25 days (daunorubicin) compared to 27 days (Idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or Idarubicin (49% ± 4% vs 55% ± 4% and 57% ± 4% vs 64% ± 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with Idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of Idarubicin than of daunorubicin during induction with a similar rate of toxicity.
Stefan Faderl - One of the best experts on this subject based on the ideXlab platform.
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a phase 1 2 study of a farnesyltransferase inhibitor tipifarnib combined with Idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high risk myelodysplastic syndrome
Cancer, 2011Co-Authors: John J. Wright, Zeev Estrov, Susan Obrien, Guillermo Garciamanero, Farhad Ravandi, Srdan Verstovsek, Elias Jabbour, Stefan FaderlAbstract:BACKGROUND: The authors conducted a phase 1/2 study of tipifarnib in combination with Idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. METHODS: Induction consisted of Idarubicin 12 mg/m2 a day on days 1-3, cytarabine 1.5 g/m2 intravenously continuously daily on days 1-4 (days 1-3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of Idarubicin 8 mg/m2 a day on days 1-2, cytarabine 0.75 g/m2 a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months. RESULTS: With a median follow-up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities. CONCLUSIONS: The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML. Cancer 2011. © 2010 American Cancer Society.
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phase i ii study of combination therapy with sorafenib Idarubicin and cytarabine in younger patients with acute myeloid leukemia
Journal of Clinical Oncology, 2010Co-Authors: Farhad Ravandi, Zeev Estrov, Stefan Faderl, Susan Obrien, Guillermo Garciamanero, Marina Konopleva, Dan Jones, Gautam BorthakurAbstract:Purpose To determine the efficacy and toxicity of the combination of sorafenib, cytarabine, and Idarubicin in patients with acute myeloid leukemia (AML) younger than age 65 years. Patients and Methods In the phase I part of the study, 10 patients with relapsed AML were treated with escalating doses of sorafenib with chemotherapy to establish the feasibility of the combination. We then treated 51 patients (median age, 53 years; range, 18 to 65 years) who had previously untreated AML with cytarabine at 1.5 g/m2 by continuous intravenous (IV) infusion daily for 4 days (3 days if > 60 years of age), Idarubicin at 12 mg/m2 IV daily for 3 days, and sorafenib at 400 mg orally twice daily for 7 days. Results Overall, 38 (75%) patients have achieved a complete remission (CR), including 14 (93%) of 15 patients with mutated FMS-like tyrosine kinase-3 (FLT3; the 15th patient had complete remission with incomplete platelet recovery [CRp]) and 24 (66%) of 36 patients with FLT3 wild-type (WT) disease (three additional F...
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clofarabine combinations as acute myeloid leukemia salvage therapy
Cancer, 2008Co-Authors: Stefan Faderl, Zeev Estrov, Alessandra Ferrajoli, Farhad Ravandi, Srdan Verstovsek, Gautam Borthakur, Xuelin Huang, William G. Wierda, Monica KwariAbstract:BACKGROUND. Outcome of patients with relapsed acute myeloid leukemia (AML) remains unsatisfactory. Clofarabine is a nucleoside analog with activity in adult AML. Combinations with cytarabine in AML are feasible and effective. Idarubicin is another active AML drug, which has not yet been tested with clofarabine. METHODS. The authors therefore designed a phase I study of clofarabinecytar- abine, plus Idarubicin. Patients with primary refractory or first-relapse AML were assigned to either clofarabine plus Idarubicin (CI) if previously exposed to cytara- bine with a response lasting <12 months, or clofarabine and Idarubicin plus cytarabine (CIA) for responses � 12 months, or if never exposed to cytarabine. A standard ''3 1 3'' phase 1 design was followed to define maximum tolerated dose (MTD). Forty-four patients were treated (23 CI; 21 CIA). RESULTS. Dose-limiting toxicities were hyperbilirubinemia and hepatic transami- nase elevations for CI-treated patients in addition to mucositis and diarrhea for CIA-treated patients. MTD for CI was clofarabine 22.5 mg/m 2 intravenously daily 3 5 and Idarubicin 10 mg/m 2 intravenously daily 3 3. MTD for CIA was clofara- bine 22.5 mg/m 2 intravenously 3 5, Idarubicin 6 mg/m 2 intravenously 3 3, and cytarabine 0.75 g/m 2 intravenously 3 5 days.
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a pilot study of imatinib low dose cytarabine and Idarubicin for patients with chronic myeloid leukemia in myeloid blast phase
Leukemia & Lymphoma, 2007Co-Authors: Alfonso Quintascardama, Stefan Faderl, Susan Obrien, Guillermo Garciamanero, Farhad Ravandi, William G. WierdaAbstract:Imatinib is the single most effective agent in chronic myelogenous leukemia (CML) in blast phase (BP), inducing hematologic responses in 30 – 50% of patients. However, only a few of these are complete (CHR) and durable. Imatinib is synergistic with Idarubicin and cytarabine. We administered imatinib 600 mg/day, cytarabine 10 mg/day subcutaneous, and Idarubicin 12 mg/m2 intravenous every 14 days in 19 patients with CML in myeloid BP. Fourteen patients (74%) achieved a hematologic response: CHR in 9 (47%) (3 with complete and 1 with minor cytogenetic responses) and return to chronic phase (RTC) in 5 (26%). Median duration of response was 10 weeks (range, 2 – 89). Six patients received allogeneic stem cell transplantation: 4 CHR, 1 chronic phase and 1 BP. Median survival was 5 months (range, 2 – 20 months). This outpatient regimen is effective and well tolerated and perhaps superior to single-agent imatinib for patients in myeloid BP.
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adaptive randomized study of Idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and Idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia
Journal of Clinical Oncology, 2003Co-Authors: Guillermo Garciamanero, Stefan Faderl, Susan Obrien, Alessandra Ferrajoli, Srdan Verstovsek, Jay K WathenAbstract:Purpose: Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with Idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy. Patients and Methods: Patients were randomized to receive Idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and Idarubicin (TI). A Bayesian design was used to adaptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients. Results: Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treat...
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improved treatment results in high risk pediatric acute myeloid leukemia patients after intensification with high dose cytarabine and mitoxantrone results of study acute myeloid leukemia berlin frankfurt munster 93
Journal of Clinical Oncology, 2001Co-Authors: U Creutzig, J. Hermann, J Ritter, M. Zimmermann, Dirk Reinhardt, Frank Berthold, G Henze, H Jurgens, H Kabisch, W HaversAbstract:PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v Idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Munster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Esti...
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improved treatment results in high risk pediatric acute myeloid leukemia patients after intensification with high dose cytarabine and mitoxantrone results of study acute myeloid leukemia berlin frankfurt munster 93
Journal of Clinical Oncology, 2001Co-Authors: U Creutzig, J. Hermann, J Ritter, M. Zimmermann, Dirk Reinhardt, Frank Berthold, G Henze, H Jurgens, H Kabisch, W HaversAbstract:PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v Idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Munster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Esti...
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Idarubicin improves blast cell clearance during induction therapy in children with aml results of study aml bfm 93
Leukemia, 2001Co-Authors: J Ritter, Blutters D Sawatzki, J. Hermann, Charlotte M. Niemeyer, Benny Selle, M. Zimmermann, Helmut Gadner, Daniel Schwabe, Joachim BoosAbstract:Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93
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Idarubicin improves blast cell clearance during induction therapy in children with aml results of study aml bfm 93
Leukemia, 2001Co-Authors: J Ritter, Blutters D Sawatzki, J. Hermann, Charlotte M. Niemeyer, Benny Selle, M. Zimmermann, Helmut Gadner, Daniel Schwabe, Joachim BoosAbstract:In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day Idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the Idarubicin arm (25 of 144 = 17% of patients with ⩾5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pχ2 = 0.01). This was, however, mainly seen in high risk patients treated with Idarubicin (19% vs 38%, Pχ2 = 0.007). Cardiotoxicity, WHO grade 1–3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/μl of 25 days (daunorubicin) compared to 27 days (Idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or Idarubicin (49% ± 4% vs 55% ± 4% and 57% ± 4% vs 64% ± 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with Idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of Idarubicin than of daunorubicin during induction with a similar rate of toxicity.
