Darbepoetin Alfa in Patients With Anemic Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

NCT01362140 | Completed Phase 3 Results DMC

• 2 other identifiers: 200901602009-016522-14
• Study Type: interventional
• Target: 147
• Locations: 9 countries
• Sites: 72

Brief Summary

The primary objective was to assess the superiority of darbepoetin alfa versus placebo on the incidence of red blood cell transfusions during the 24-week double-blind treatment period in anemic patients with low or intermediate-1 risk MDS.

Conditions

MDS

Keywords

Randomized; Darbepoetin alfa; Myelodysplastic Syndromes; Placebo-controlled; low risk MDS; intermediate-1 risk MDS; International Prognostic Scoring System

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least One Red Blood Cell (RBC) Transfusion During the Double-blind Treatment Period

  Week 5 to Week 25

Secondary Outcomes (8)

• Percentage of Participants Who Achieved an Erythroid Response Based on International Working Group (IWG) 2006 Criteria in the Double-blind Treatment Period

  Up to 24 weeks

• Number of Participants With Adverse Events

  From first dose of study drug until the end of the double-blind treatment period; 24 weeks.

• Number of Participants With Disease Progression to Acute Myeloid Leukemia (AML)

  24 weeks

• Number of Participants With Malignancies Other Than AML, Basal Cell Carcinoma, or Squamous Cell Carcinoma of the Skin

  Up to 24 weeks

• Number of Participants Who Developed Neutralizing Antibodies to Darbepoetin Alfa

  Baseline and end of double-blind treatment period (24 weeks)

Study Arms (2)

Darbepoetin alfa

EXPERIMENTAL

Participants received darbepoetin alfa 500 µg every three weeks (Q3W) for 24 weeks in the double-blind treatment period, and continued to receive darbepoetin alfa 500 µg Q3W during the active treatment period for an additional 48 weeks.

Drug: Darbepoetin alfa

Placebo

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks during the double-blind treatment period. From week 25 participants received darbepoetin alfa 500 µg Q3W during the active treatment period for 48 weeks.

Drug: Placebo

Interventions

Darbepoetin alfa DRUG

Administered by subcutaneous injection every 3 weeks

Also known as: Aranesp

Darbepoetin alfa

Placebo DRUG

Administered by subcutaneous injection every 3 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Low or intermediate-1 risk MDS patients per International Prognostic Scoring System (IPSS) at the time of randomisation, as determined by complete blood count (CBC) during screening and bone marrow examination and marrow cytogenetic analysis performed within 16 weeks prior to randomisation. Subject cannot have been rendered low or intermediate-1 risk by prior disease modifying therapy. Bone marrow slides must be available for centralized review at any time throughout the study
• World Health Organization (WHO) classification of refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory cytopenias with multilineage dysplasia (RCMD), MDS-unclassified (MDSU), MDS with isolated del(5q) (5q- syndrome) or refractory anaemia with excess blasts-1 (RAEB-1)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 assessed during screening
• Haemoglobin level ≤ 10.0 g/dL as assessed by the local laboratory; sample obtained within 7 days prior to randomisation (retest during screening is acceptable)
• Adequate transferrin saturation (Tsat) (≥ 15%) and serum ferritin (≥ 10 ng/mL) as assessed by the central laboratory during screening (supplementation and retest during screening is acceptable)
• Adequate serum folate (≥ 4.5 nmol/L \[≥ 2.0 ng/mL\]) or RBC folate (≥ 317 nmol/L \[≥ 140 ng/mL\]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable)
• Adequate vitamin B12 (≥ 148 pmol/L \[≥ 200 pg/mL\]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable)
• years of age or older
• Subject or subject's legally acceptable representative has provided informed consent -

You may not qualify if:

• Previously diagnosed with intermediate-2 or high risk MDS per IPSS
• Therapy-related or secondary MDS
• History of acute leukemia
• Evidence of bone marrow collagen fibrosis
• Inherited anaemia (eg, haemoglobinopathy, thalassemia, red cell membrane defect, red cell enzyme deficiency), active hemorrhage, red cell aplasia, haemolytic anaemia
• History of malignancies other than curatively treated non-melanoma skin or in situ carcinoma
• History of thrombosis within 6 months prior to randomisation
• Previous bone marrow or stem cell transplantation
• Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to randomisation
• Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at screening
• Clinically significant systemic infection or uncontrolled chronic inflammatory disease (ie, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator at screening
• History of seizure disorder (subject with previous history of seizure disorder will be eligible for the study if he/she had no evidence of seizure activity within 5 years of randomisation and is currently free of antiseizure medication)
• Previous or ongoing use of erythropoiesis-stimulating agent (ESA) therapy, eg, recombinant human erythropoietin (rHuEpo), darbepoetin alfa
• High transfusion demand: receiving a total of ≥ 4 units of RBC transfusion during either of 2 consecutive 8-week periods (ie, days -113 to -57 or days -56 to 0) prior to randomisation
• Received any RBC transfusion within 14 days prior to randomisation

Sponsors & Collaborators

• Amgen: lead

Study Sites (72)

Research Site

Innsbruck, 6020, Austria

Location

Research Site

Linz, 4020, Austria

Location

Research Site

Salzburg, 5020, Austria

Location

Research Site

Vienna, 1140, Austria

Location

Research Site

Bruges, 8000, Belgium

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

Charleroi, 6000, Belgium

Location

Research Site

Ghent, 9000, Belgium

Location

Research Site

Haine Saint Paul - La Louviere, 7100, Belgium

Location

Research Site

Hasselt, 3500, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Liège, 4000, Belgium

Location

Research Site

Ottignies, 1340, Belgium

Location

Research Site

Roeselare, 8800, Belgium

Location

Research Site

Sint-Niklaas, 9100, Belgium

Location

Research Site

Brno, 625 00, Czechia

Location

Research Site

Hradec Králové, 500 05, Czechia

Location

Research Site

Olomouc, 775 20, Czechia

Location

Research Site

Ostrava-Poruba, 708 52, Czechia

Location

Research Site

Prague, 100 34, Czechia

Location

Research Site

Prague, 128 08, Czechia

Location

Research Site

Prague, 128 20, Czechia

Location

Research Site

Prague, 150 06, Czechia

Location

Research Site

Zlín, 760 01, Czechia

Location

Research Site

Avignon, 84902, France

Location

Research Site

Bobigny, 93009, France

Location

Research Site

Caen, 14033, France

Location

Research Site

Lyon, 69009, France

Location

Research Site

Lyon Cédex 3, 69437, France

Location

Research Site

Nantes, 44035, France

Location

Research Site

Nice, 06202, France

Location

Research Site

Paris, 75015, France

Location

Research Site

Paris, 75475, France

Location

Research Site

Pontoise, 95301, France

Location

Research Site

Toulouse, 31059, France

Location

Research Site

Vandœuvre-lès-Nancy, 54511, France

Location

Research Site

Cologne, 50677, Germany

Location

Research Site

Dresden, 01307, Germany

Location

Research Site

Göttingen, 37075, Germany

Location

Research Site

Hanover, 30625, Germany

Location

Research Site

Leipzig, 04103, Germany

Location

Research Site

Mannheim, 68167, Germany

Location

Research Site

Regensburg, 93053, Germany

Location

Research Site

Rotenburg (Wümme), 27356, Germany

Location

Research Site

Ulm, 89081, Germany

Location

Research Site

Athens, 11527, Greece

Location

Research Site

Athens, 12462, Greece

Location

Research Site

Ioannina, 45110, Greece

Location

Research Site

Pátrai, 26500, Greece

Location

Research Site

Thessaloniki, 57010, Greece

Location

Research Site

Alessandria, 15100, Italy

Location

Research Site

Bologna, 40138, Italy

Location

Research Site

Genova, 16132, Italy

Location

Research Site

Milan, 20122, Italy

Location

Research Site

Palermo, 90146, Italy

Location

Research Site

Pavia, 27100, Italy

Location

Research Site

Pesaro, 61100, Italy

Location

Research Site

Pisa, 56127, Italy

Location

Research Site

Reggio Calabria, 89124, Italy

Location

Research Site

Rionero in Vulture PZ, 85028, Italy

Location

Research Site

Roma, 00161, Italy

Location

Research Site

San Giovanni Rotondo FG, 71013, Italy

Location

Research Site

Udine, 33100, Italy

Location

Research Site

Zaragoza, Aragon, 50009, Spain

Location

Research Site

Salamanca, Castille and León, 37007, Spain

Location

Research Site

Barcelona, Catalonia, 08003, Spain

Location

Research Site

Valencia, Valencia, 46010, Spain

Location

Research Site

Valencia, Valencia, 46026, Spain

Location

Research Site

Basel, 4031, Switzerland

Location

Research Site

Lucerne, 6000, Switzerland

Location

Research Site

Muensterlingen, 8596, Switzerland

Location

Research Site

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J, Slama B, Badre S, Gasal E, Mehta B, Franklin J. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017 Sep;31(9):1944-1950. doi: 10.1038/leu.2017.192. Epub 2017 Jun 19.

  PMID: 28626220 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Darbepoetin alfa

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2011
• First Posted: May 30, 2011
• Study Start: December 21, 2011
• Primary Completion: February 11, 2015
• Study Completion: September 14, 2017
• Last Updated: December 19, 2017
• Results First Posted: December 5, 2016

Record last verified: 2017-11

Locations

DE (9); IT (13); CZ (9); BE (11); ES (5); AU (4); GR (5); FR (12); CH (4)