ARCADE (20090160): A PHASE 3 RANDOMIZED PLACEBO-CONTROLLED DOUBLE-BLIND TRIAL OF DARBEPOETIN ALFA IN THE TREATMENT OF ANEMIA IN PATIENTS WITH LOW OR INTERMEDIATE-1 RISK MYELODYSPLASTIC SYNDROMES (MDS)
(Abstract release date: 05/19/16)
EHA Library. Platzbecker U. 06/10/16; 135161; S128
Prof. Dr. Uwe Platzbecker
Contributions
Contributions
Abstract
Abstract: S128
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Hall C14
Background
Although erythropoiesis-stimulating agents (ESAs) are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, ESAs are not widely approved for this indication.
Aims
To evaluate the efficacy and safety of darbepoetin alfa (DAR) in IPSS low / intermediate-1 (int-1) risk MDS patients with anemia, in a phase 3, randomized, placebo(PBO)-controlled trial (EudraCT#2009-016522-14, NCT#01362140).
Methods
Patients were enrolled from Dec 21, 2011 to Aug 27, 2014 in 9 European countries. Eligible patients had low/int-1 MDS, anemia [hemoglobin (Hgb) ≤10 g/dL], low transfusion burden (<4 transfusion units in each of 2 consecutive 8-week periods prior to randomization), no previous treatment with ESAs or biologic‑response modifiers, and endogenous erythropoietin (EPO) levels ≤500 mU/mL. Patients were randomized 2:1 to receive 24 weeks of subcutaneous DAR 500 µg or PBO every 3 weeks (Q3W), stratified by IPSS status (low or int-1). The dose was reduced if Hgb was >12.0 g/dL or if Hgb increased by >1.5 g/dL in 3 weeks without transfusion. Investigational product (IP) was discontinued and the patient entered follow-up if >3 dose reductions were needed. Key efficacy endpoints included (1) transfusion incidence from weeks 5-24 and (2) erythroid response (HI‑E) per IWG 2006 criteria, ie, ≥1.5 g/dL increase from baseline in Hgb with a mean rise of ≥1.5 g/dL for 8 weeks without transfusions. Results from the 24-week double-blind period are reported here; patients could then receive open-label DAR 500 µg Q3W for 48 weeks and were followed up for survival and progression to AML status for up to 3 years (ongoing).
Results
A total of 147 patients were randomized; 50.7% of patients were IPSS low risk and 49.3% were int‑1 risk, median Hgb levels were 9.3 (Q1:8.8, Q3:9.7) g/dL, median EPO levels were 69 (Q1:36, Q3:158) mU/mL, rates of good / intermediate / poor IPSS karyotype were 91% / 9% / 0%, respectively, and % WHO classifications were RA:15%, RARS:14%, RCMD:44%, del5q:9%, RAEB-1:16%, and MDS‑U/unknown:2%. There were 146 (97 DAR, 49 PBO) patients in the primary analysis set. Baseline demographic and disease characteristics were generally similar between the two arms. Transfusion incidence from weeks 5-24 was significantly reduced with DAR vs. PBO (DAR:36.1% vs. PBO:59.2%, p=0.008). The proportion achieving HI-E was significantly increased with DAR vs. PBO; DAR:14.7% (11 of 75 evaluable) vs. PBO:0% (0 of 35 evaluable), p=0.016. All patients with HI-E (n=11) had a baseline serum EPO level <100 mU/mL. Adverse events (AEs) occurring ≥5% more frequently in the DAR arm than the PBO arm were fatigue, pyrexia, headache, and myalgia. Safety results from this trial were consistent with the previous DAR phase 2 MDS trial (Gabrilove BJH 2008, 142:379-393).
Conclusion
In this phase 3, randomized, double-blind, PBO-controlled trial in low/int-1 MDS patients with anemia, 24 weeks of DAR Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals.
Session topic: Myelodysplastic syndromes - Clinical
Keyword(s): Anemia, Erythropoieisis, Transfusion
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Hall C14
Background
Although erythropoiesis-stimulating agents (ESAs) are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, ESAs are not widely approved for this indication.
Aims
To evaluate the efficacy and safety of darbepoetin alfa (DAR) in IPSS low / intermediate-1 (int-1) risk MDS patients with anemia, in a phase 3, randomized, placebo(PBO)-controlled trial (EudraCT#2009-016522-14, NCT#01362140).
Methods
Patients were enrolled from Dec 21, 2011 to Aug 27, 2014 in 9 European countries. Eligible patients had low/int-1 MDS, anemia [hemoglobin (Hgb) ≤10 g/dL], low transfusion burden (<4 transfusion units in each of 2 consecutive 8-week periods prior to randomization), no previous treatment with ESAs or biologic‑response modifiers, and endogenous erythropoietin (EPO) levels ≤500 mU/mL. Patients were randomized 2:1 to receive 24 weeks of subcutaneous DAR 500 µg or PBO every 3 weeks (Q3W), stratified by IPSS status (low or int-1). The dose was reduced if Hgb was >12.0 g/dL or if Hgb increased by >1.5 g/dL in 3 weeks without transfusion. Investigational product (IP) was discontinued and the patient entered follow-up if >3 dose reductions were needed. Key efficacy endpoints included (1) transfusion incidence from weeks 5-24 and (2) erythroid response (HI‑E) per IWG 2006 criteria, ie, ≥1.5 g/dL increase from baseline in Hgb with a mean rise of ≥1.5 g/dL for 8 weeks without transfusions. Results from the 24-week double-blind period are reported here; patients could then receive open-label DAR 500 µg Q3W for 48 weeks and were followed up for survival and progression to AML status for up to 3 years (ongoing).
Results
A total of 147 patients were randomized; 50.7% of patients were IPSS low risk and 49.3% were int‑1 risk, median Hgb levels were 9.3 (Q1:8.8, Q3:9.7) g/dL, median EPO levels were 69 (Q1:36, Q3:158) mU/mL, rates of good / intermediate / poor IPSS karyotype were 91% / 9% / 0%, respectively, and % WHO classifications were RA:15%, RARS:14%, RCMD:44%, del5q:9%, RAEB-1:16%, and MDS‑U/unknown:2%. There were 146 (97 DAR, 49 PBO) patients in the primary analysis set. Baseline demographic and disease characteristics were generally similar between the two arms. Transfusion incidence from weeks 5-24 was significantly reduced with DAR vs. PBO (DAR:36.1% vs. PBO:59.2%, p=0.008). The proportion achieving HI-E was significantly increased with DAR vs. PBO; DAR:14.7% (11 of 75 evaluable) vs. PBO:0% (0 of 35 evaluable), p=0.016. All patients with HI-E (n=11) had a baseline serum EPO level <100 mU/mL. Adverse events (AEs) occurring ≥5% more frequently in the DAR arm than the PBO arm were fatigue, pyrexia, headache, and myalgia. Safety results from this trial were consistent with the previous DAR phase 2 MDS trial (Gabrilove BJH 2008, 142:379-393).
| Placebo (N=48), n (%) | Darbepoetin alfa (N=98), n (%) | |
| AEs leading to IP discontinuation | 2 (4.2) | 3 (3.1) |
| Grade ≥3 / grade ≥4 | 13 (27.1) / 6 (12.5) | 15 (15.3) / 5 (5.1) |
| Fatal AEs (none treatment-related) | 2 (4.2) | 1 (1.0) |
| Serious AEs | 8 (16.7) | 11 (11.2) |
| Treatment-related serious AEs | 0 (0) | 1 (1.0) |
| Venous thromboembolic events | 0 (0) | 1 (1.0) |
| Progression to AML | 1 (2.2) | 2 (2.1) |
Conclusion
In this phase 3, randomized, double-blind, PBO-controlled trial in low/int-1 MDS patients with anemia, 24 weeks of DAR Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals.
Session topic: Myelodysplastic syndromes - Clinical
Keyword(s): Anemia, Erythropoieisis, Transfusion
Abstract: S128
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Hall C14
Background
Although erythropoiesis-stimulating agents (ESAs) are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, ESAs are not widely approved for this indication.
Aims
To evaluate the efficacy and safety of darbepoetin alfa (DAR) in IPSS low / intermediate-1 (int-1) risk MDS patients with anemia, in a phase 3, randomized, placebo(PBO)-controlled trial (EudraCT#2009-016522-14, NCT#01362140).
Methods
Patients were enrolled from Dec 21, 2011 to Aug 27, 2014 in 9 European countries. Eligible patients had low/int-1 MDS, anemia [hemoglobin (Hgb) ≤10 g/dL], low transfusion burden (<4 transfusion units in each of 2 consecutive 8-week periods prior to randomization), no previous treatment with ESAs or biologic‑response modifiers, and endogenous erythropoietin (EPO) levels ≤500 mU/mL. Patients were randomized 2:1 to receive 24 weeks of subcutaneous DAR 500 µg or PBO every 3 weeks (Q3W), stratified by IPSS status (low or int-1). The dose was reduced if Hgb was >12.0 g/dL or if Hgb increased by >1.5 g/dL in 3 weeks without transfusion. Investigational product (IP) was discontinued and the patient entered follow-up if >3 dose reductions were needed. Key efficacy endpoints included (1) transfusion incidence from weeks 5-24 and (2) erythroid response (HI‑E) per IWG 2006 criteria, ie, ≥1.5 g/dL increase from baseline in Hgb with a mean rise of ≥1.5 g/dL for 8 weeks without transfusions. Results from the 24-week double-blind period are reported here; patients could then receive open-label DAR 500 µg Q3W for 48 weeks and were followed up for survival and progression to AML status for up to 3 years (ongoing).
Results
A total of 147 patients were randomized; 50.7% of patients were IPSS low risk and 49.3% were int‑1 risk, median Hgb levels were 9.3 (Q1:8.8, Q3:9.7) g/dL, median EPO levels were 69 (Q1:36, Q3:158) mU/mL, rates of good / intermediate / poor IPSS karyotype were 91% / 9% / 0%, respectively, and % WHO classifications were RA:15%, RARS:14%, RCMD:44%, del5q:9%, RAEB-1:16%, and MDS‑U/unknown:2%. There were 146 (97 DAR, 49 PBO) patients in the primary analysis set. Baseline demographic and disease characteristics were generally similar between the two arms. Transfusion incidence from weeks 5-24 was significantly reduced with DAR vs. PBO (DAR:36.1% vs. PBO:59.2%, p=0.008). The proportion achieving HI-E was significantly increased with DAR vs. PBO; DAR:14.7% (11 of 75 evaluable) vs. PBO:0% (0 of 35 evaluable), p=0.016. All patients with HI-E (n=11) had a baseline serum EPO level <100 mU/mL. Adverse events (AEs) occurring ≥5% more frequently in the DAR arm than the PBO arm were fatigue, pyrexia, headache, and myalgia. Safety results from this trial were consistent with the previous DAR phase 2 MDS trial (Gabrilove BJH 2008, 142:379-393).
Conclusion
In this phase 3, randomized, double-blind, PBO-controlled trial in low/int-1 MDS patients with anemia, 24 weeks of DAR Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals.
Session topic: Myelodysplastic syndromes - Clinical
Keyword(s): Anemia, Erythropoieisis, Transfusion
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Hall C14
Background
Although erythropoiesis-stimulating agents (ESAs) are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, ESAs are not widely approved for this indication.
Aims
To evaluate the efficacy and safety of darbepoetin alfa (DAR) in IPSS low / intermediate-1 (int-1) risk MDS patients with anemia, in a phase 3, randomized, placebo(PBO)-controlled trial (EudraCT#2009-016522-14, NCT#01362140).
Methods
Patients were enrolled from Dec 21, 2011 to Aug 27, 2014 in 9 European countries. Eligible patients had low/int-1 MDS, anemia [hemoglobin (Hgb) ≤10 g/dL], low transfusion burden (<4 transfusion units in each of 2 consecutive 8-week periods prior to randomization), no previous treatment with ESAs or biologic‑response modifiers, and endogenous erythropoietin (EPO) levels ≤500 mU/mL. Patients were randomized 2:1 to receive 24 weeks of subcutaneous DAR 500 µg or PBO every 3 weeks (Q3W), stratified by IPSS status (low or int-1). The dose was reduced if Hgb was >12.0 g/dL or if Hgb increased by >1.5 g/dL in 3 weeks without transfusion. Investigational product (IP) was discontinued and the patient entered follow-up if >3 dose reductions were needed. Key efficacy endpoints included (1) transfusion incidence from weeks 5-24 and (2) erythroid response (HI‑E) per IWG 2006 criteria, ie, ≥1.5 g/dL increase from baseline in Hgb with a mean rise of ≥1.5 g/dL for 8 weeks without transfusions. Results from the 24-week double-blind period are reported here; patients could then receive open-label DAR 500 µg Q3W for 48 weeks and were followed up for survival and progression to AML status for up to 3 years (ongoing).
Results
A total of 147 patients were randomized; 50.7% of patients were IPSS low risk and 49.3% were int‑1 risk, median Hgb levels were 9.3 (Q1:8.8, Q3:9.7) g/dL, median EPO levels were 69 (Q1:36, Q3:158) mU/mL, rates of good / intermediate / poor IPSS karyotype were 91% / 9% / 0%, respectively, and % WHO classifications were RA:15%, RARS:14%, RCMD:44%, del5q:9%, RAEB-1:16%, and MDS‑U/unknown:2%. There were 146 (97 DAR, 49 PBO) patients in the primary analysis set. Baseline demographic and disease characteristics were generally similar between the two arms. Transfusion incidence from weeks 5-24 was significantly reduced with DAR vs. PBO (DAR:36.1% vs. PBO:59.2%, p=0.008). The proportion achieving HI-E was significantly increased with DAR vs. PBO; DAR:14.7% (11 of 75 evaluable) vs. PBO:0% (0 of 35 evaluable), p=0.016. All patients with HI-E (n=11) had a baseline serum EPO level <100 mU/mL. Adverse events (AEs) occurring ≥5% more frequently in the DAR arm than the PBO arm were fatigue, pyrexia, headache, and myalgia. Safety results from this trial were consistent with the previous DAR phase 2 MDS trial (Gabrilove BJH 2008, 142:379-393).
| Placebo (N=48), n (%) | Darbepoetin alfa (N=98), n (%) | |
| AEs leading to IP discontinuation | 2 (4.2) | 3 (3.1) |
| Grade ≥3 / grade ≥4 | 13 (27.1) / 6 (12.5) | 15 (15.3) / 5 (5.1) |
| Fatal AEs (none treatment-related) | 2 (4.2) | 1 (1.0) |
| Serious AEs | 8 (16.7) | 11 (11.2) |
| Treatment-related serious AEs | 0 (0) | 1 (1.0) |
| Venous thromboembolic events | 0 (0) | 1 (1.0) |
| Progression to AML | 1 (2.2) | 2 (2.1) |
Conclusion
In this phase 3, randomized, double-blind, PBO-controlled trial in low/int-1 MDS patients with anemia, 24 weeks of DAR Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals.
Session topic: Myelodysplastic syndromes - Clinical
Keyword(s): Anemia, Erythropoieisis, Transfusion
{{ help_message }}
{{filter}}