scholarly journals A Post Hoc Sensitivity Analysis of Survival Probabilities in a Multinational Phase III Trial of Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

2014 ◽  
Vol 14 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Xavier G. Thomas ◽  
Christopher Arthur ◽  
Jacques Delaunay ◽  
Mark Jones ◽  
Erhan Berrak ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Survival Probabilities ◽  
Post Hoc ◽  
Acute Myeloid

scholarly journals Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia

2012 ◽  
Vol 30 (21) ◽  
pp. 2670-2677 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Xavier G. Thomas ◽  
Anna Dmoszynska ◽  
Agnieszka Wierzbowska ◽  
Grzegorz Mazur ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Primary Analysis ◽  
Open Label ◽  
Phase Iii Trial ◽  
Open Label Phase ◽  
Acute Myeloid

Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). Conclusion In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis.

scholarly journals Post hoc analysis of relationship between baseline white blood cell count and survival outcome in a randomized phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6559-6559
Author(s):  
Chris Arthur ◽  
Jaroslav Cermak ◽  
Jacques Delaunay ◽  
Jiri Mayer ◽  
Grzegorz Mazur ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Survival Outcome ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Post Hoc Analysis ◽  
Wbc Count ◽  
Post Hoc ◽  
Acute Myeloid

6559 Background: In a large phase III trial (N=485), patients (pts) ≥65y with newly diagnosed acute myeloid leukemia (AML) received 1-h IV infusion of decitabine (DAC) 20 mg/m2 for 5 consecutive days every 4 wk or treatment choice (TC) with supportive care or cytarabine 20 mg/m2 subcutaneous injection for 10 consecutive days every 4 wk (NCT00260832; Kantarjian et al. JCO, in press). Enrolled pts had white blood cell (WBC) count <40 x109/L; baseline WBC counts were relatively low (median [range] DAC: 3.1 x109/L [0.3-127.0]; TC: 3.7 x109/L [0.5-80.9]). This post hoc analysis assessed baseline WBC count and survival outcome. Methods: Overall survival (OS) and progression-free survival (PFS) were summarized by baseline WBC subgroups (<1, 1-5, >5 x109/L). Results: Mature survival data (2010) were based on intent-to-treat (ITT) population (446 deaths: TC, n=227; DAC, n=219). OS was 5.0 mo for TC vs 7.7 mo for DAC (nominal P=.037). For each WBC subgroup, differences in OS for TC vs DAC were not significant (NS), but hazard ratios (HR) favored DAC for all subgroups (Table). There was a significant difference in PFS in favor of DAC for patients with baseline WBC 1–5 x109/L (P=.005; HR=0.67) and >5 x109/L (P=.027; HR=0.71). Conclusions: These data are consistent with overall results, with a trend toward improved outcome with DAC regardless of baseline WBC count in older pts with newly diagnosed AML. Further analyses are warranted. [Table: see text]

Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17)

2013 ◽  
Vol 31 (35) ◽  
pp. 4424-4430 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Roberto Stasi ◽  
Helmut R. Salih ◽  
Dominik Selleslag ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Sequential Combination ◽  
Grade 3 ◽  
Acute Myeloid

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m2 on day 0). The primary end point was overall survival (OS). Results The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality. Conclusion As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

scholarly journals CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

2018 ◽  
Vol 36 (26) ◽  
pp. 2684-2692 ◽  
Author(s):  
Jeffrey E. Lancet ◽  
Geoffrey L. Uy ◽  
Jorge E. Cortes ◽  
Laura F. Newell ◽  
Tara L. Lin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Remission Rate ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

Post hoc analysis of relationship between baseline white blood cell count and renal and hepatic function and response in a randomized phase III trial of decitabine in patients age 65 or older with acute myeloid leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6632-6632
Author(s):  
Jacques Delaunay ◽  
Grzegorz Mazur ◽  
Mark D Minden ◽  
Agnieszka Wierzbowska ◽  
Mark M. Jones ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Blood Cell ◽  
White Blood Cell ◽  
Myeloid Leukemia ◽  
Hepatic Function ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Acute Myeloid

6632 Background: A phase III trial (NCT00260832) in patients (N=485) ≥65y with newly diagnosed acute myeloid leukemia (AML) was conducted (Kantarjian, JCO; in press). Every 4 wk, patients received decitabine (DAC) 20 mg/m2 (1-h intravenous infusion, 5 successive days) or treatment choice (TC) with either supportive care or cytarabine (20 mg/m2 subcutaneous injection daily, 10 successive days). This post hoc analysis examined whether baseline (BL) renal and hepatic function and white blood cell (WBC) counts were associated with response to DAC or TC. Methods: For patients with available data, BL WBC count and markers of renal function (blood urea nitrogen [BUN], creatinine) and liver function (ALT, AST, albumin) were tabulated for patients with/without a response to DAC or TC. Response was defined as morphologic complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR). Results: Nonresponders had a higher mean BL creatinine vs responders (86.78 vs 80.23 mmol/L, respectively; P=.005); with no differences in BL BUN levels. There were no other between-group differences. Conclusions: This analysis suggests that there is no relationship between BL WBC or hepatic function and response to treatment with DAC or TC. Although there was no difference in BL BUN, higher mean creatinine levels in nonresponders may suggest a prognostic relationship but further studies are needed to clarify. [Table: see text]

Post hoc analysis of association between treatment response and various indicators of efficacy and safety in a randomized phase III trial of decitabine in older patients with acute myeloid leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6627-6627
Author(s):  
Mark D Minden ◽  
Chris Arthur ◽  
Jiri Mayer ◽  
Mark M. Jones ◽  
Peter G. Tarassoff ◽  
...  
Keyword(s):  
Older Patients ◽  
Myeloid Leukemia ◽  
Antibiotic Use ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Phase Iii Trial ◽  
Post Hoc Analysis ◽  
Dose Modifications ◽  
Post Hoc

6627 Background: In a recent, large phase III trial (NCT00260832; Kantarjian, JCO; in press), 485 patients ≥65y with newly diagnosed acute myeloid leukemia (AML) received, every 4 wks, treatment choice (TC) of either supportive care or cytarabine (20 mg/m2 subcutaneous injection, 10 consecutive days) or decitabine (DAC) 20 mg/m2 (1-h intravenous [IV] infusion, 5 consecutive days). This post hoc analysis investigated relationships between response to treatment and indicators of efficacy and safety. Methods: Response was defined as morphologic complete remission (CR), or CR with incomplete blood count recovery (CRi) or partial response (PR). Transfusions (red blood cell [RBC] or platelets [PLT]), IV antibiotic use, and dose modifications were tabulated for responders and nonresponders to DAC or TC during the treatment period. Results: Fewer responders than nonresponders had dose modifications (30.4% vs 64.5%, respectively; P<.0001). Antibiotic use and transfusions were similar in both groups. Overall survival for responders was 16.1–18.5 mo vs 4.2–4.9 mo for nonresponders. Conclusions: These data suggest that response to DAC or TC treatment predicts clinically relevant benefits, with fewer dose modifications in older patients with newly diagnosed AML. The number of transfusions and antibiotic use was impacted by the longer survival time of responders vs nonresponders. Data on the impact of early response are being analyzed. [Table: see text]

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