scholarly journals Analysis of Transplantation Rate and Overall Treatment Efficacy by Age for Patients Aged 60 to 75 with Untreated Secondary Acute Myeloid Leukemia (AML) Given CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial

2017 ◽  
Vol 23 (3) ◽  
pp. S38-S39 ◽  
Author(s):  
Jeffery Lancet ◽  
Geoffrey L. Uy ◽  
Jorge Cortes ◽  
Laura F. Newell ◽  
Tara L. Lin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Efficacy ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

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.

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.

Remission Rates In Childhood Acute Myeloid Leukemia (AML) Utilizing a Dose-Intensive Induction Regimen with or without Gemtuzumab Ozogamicin (GO): Initial Results From the Children's Oncology Group Phase III Trial, AAML0531

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 182-182 ◽  
Author(s):  
Alan S Gamis ◽  
Todd A Alonzo ◽  
Robert B Gerbing ◽  
Richard Aplenc ◽  
Lillian Sung ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Diagnostic Characteristics ◽  
Significant Difference ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 182 Acute Myeloid Leukemia - Therapy, excluding Transplantation: Pediatric and Adult AML Therapy Therapy for childhood AML has evolved in North America over the past decade by pursuing a dose-intensive rather than an intensive-timing strategy. COG AAML0531 was a recently completed Phase III trial that was based upon the MRC AML 12 dose-intensive regimen which reported a complete remission (CR) rate of 93% in their ADE arm with 3% induction (Ind) deaths (Gibson, Blood 100:35a, 2002). While survival outcomes remain “blinded” as the last patients (pts) complete therapy, remission (REM) outcomes can now be examined. Utilizing a data cutoff of March 31, 2010, 1009 non-M3 AML pts were enrolled and after excluding 36 ineligible and 5 DS pts 968 eligible de novo AML were examined. Pts were randomized to standard therapy with or without GO at 3 mg/m2 given on Ind I day 6 and intensification II day 7. Induction consisted of 2 therapy courses (Ind I: ADE10 & Ind II: ADE8), cytarabine 100 mg/m2/dose bid × 10 days (8 days for Ind II), etoposide 100 mg/m2/day on days 1–5, and daunomycin 50 mg/m2/day on days 1–3-5. Pts remained on the trial regardless of REM status after Ind I; however pts not in CR after Ind II were taken off protocol. There were 968 pts that began Ind I and 851 pts that began Ind II, with 25 & 7 withdrawals, 50 & 29 who were still in Ind or had not yet submitted data, and 19 & 4 deaths in each course, respectively. CR (defined in the protocol as <5% morphologic blasts (blasts) & extramedullary disease (EMD) resolved) was achieved in 70% (628/900) & 86% (731/854) by the end of each Ind course, respectively. This is similar to that seen in the intensively-timed CCG-2961 after 2 Ind courses. The impact of REM status after Ind I upon CR rates after Ind II was then assessed. After Ind I (ADE10), partial REM (PR) (5-15% blasts) was seen in 12% (104/900) and persistent disease (PD) (>15% blasts) was seen in 14% (126/900) of whom 81% (79/98) & 60% (65/109) entered CR after Ind II (ADE8), respectively. The extent of PD after Ind I and its impact upon CR after Ind II was then examined. For those whose PD was defined by only residual EMD and whose marrow was in PR or CR, 97% achieved a CR after Ind II. For those whose PD was defined by marrow blasts >15%, 42% achieved CR following Ind II. We examined whether the degree of marrow disease (15-30% vs >30% blasts) impacted CR in the PD pts but found no significant difference in CR by amount of PD (52% vs 36%, p=.234). Among the 25 pts who withdrew from Ind I, response after Ind I was assessable in 19 (4 CR, 1 PR, 14 PD) although no impact upon Ind II outcome could be ascertained. Diagnostic characteristics were analyzed for CR rate after Ind II with selected risk factors listed in the table. Significant prognostic factors for REM after 2 courses were found by univariate analysis to include WBC>100,000 (OR=2.7, p<.001), FLT3-ITD (OR=2.9, p<.001), low risk cytogenetics (OR=0.2, p<.001). In a multivariate model in 464 pts who had all three risk factors reported to date, the same risk factors were independently predictive of outcome: WBC (OR=2.5, p=.002), FLT3-ITD (OR = 2.0, p=.034), and low risk cytogenetics (OR = 0.24, p=.007). FLT3 analysis for this abstract includes only those clinically available (after a trial amendment in the 3rd year). This will be updated with the FLT3 research sample analyses for those pts enrolled prior to the amendment. Overall toxic mortality by the end of Ind II of 2.7% (2.1% in ADE10, and 0.5% in ADE8) are similar to reported outcomes in the COG pilot trial, AAML03P1, (2.6%) and better than that seen in CCG-2961 (14.1% & 10%, pre-& post-amendment). These data provide an important background for the next COG Phase III trial utilizing this same standard Ind due to open soon and provides a platform for an early comparison between outcomes of the MRC trials and those in COG with identical Ind courses. Disclosures: Smith: Pfizer, Inc: Member, Medical Advisory Committee (for bosutinib—not GO).

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]

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