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

NCT ID: NCT01362140

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-21
• Study Completion Date: 2017-09-14

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.

Detailed Description

This study consists of a 3-week screening period, a 24-week double-blind treatment period, and a 48-week active treatment period and the long-term follow-up period.

An end of treatment period (EOTP) visit occurs at week 25, or 3 weeks after last dose of investigational product (IP) for participants who withdraw from the study. After entering the active treatment period, an end of active treatment period (EOATP) visit occurs at week 72 / 73, or 3 weeks after the last dose of darbepoetin alfa.

Long-term follow-up (LTFU) will occur every 26 weeks (± 4 weeks) from the EOATP visit (or EOTP visit if the participant does not enter the active treatment period) and will continue for a minimum of 3 years from the first dose of IP. Follow-up may occur through clinic visit or telephone contacts. Information on the participant's survival and progression to AML status will be collected during LTFU.

Conditions

MDS

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Darbepoetin alfa

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.

Group Type: EXPERIMENTAL

Darbepoetin alfa

Intervention Type: DRUG

Administered by subcutaneous injection every 3 weeks

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered by subcutaneous injection every 3 weeks

Interventions

Darbepoetin alfa

Administered by subcutaneous injection every 3 weeks

Intervention Type: DRUG

Placebo

Administered by subcutaneous injection every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Aranesp

Eligibility Criteria

Inclusion Criteria

• 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)
• 18 years of age or older
• Subject or subject's legally acceptable representative has provided informed consent -

Exclusion Criteria

• 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
• Received cytotoxic chemotherapy for any oncologic indication or planning to receive cytotoxic chemotherapy during the double-blind treatment period of the study
• Received biologic response modifiers (eg, thalidomide, lenalidomide, arsenic trioxide, azacitidine, decitabine) to treat MDS or planning to receive biologic response modifiers during the double-blind treatment period of the study
• Received myeloablative or craniospinal radiation or planning to receive myeloablative or craniospinal radiation during the double-blind treatment period of the study
• Received granulocyte colony stimulating factor (G-CSF) therapy within 30 days prior to randomization or planning to receive G-CSF therapy during the double-blind treatment period of the study (temporary use of G-CSF for neutropenia with fever and/or infection is acceptable)
• Abnormal renal function (serum creatinine level > 2 times the upper limit of the respective normal range [ULN]) as assessed by the central laboratory at screening
• Abnormal liver function (total bilirubin > 2 times, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times ULN) as assessed by the central laboratory at screening. (Subjects with abnormal bilirubin at screening due to documented Gilbert's Disease are eligible if all other criteria are met.)
• Serum endogenous erythropoetin (EPO) level > 500 mU/mL as assessed by the central laboratory at screening
• Known seropositivity for human immunodeficiency virus (HIV) or diagnosis of acquired Immunodeficiency syndrome (AIDS), positive for hepatitis B surface antigen, or seropositive for hepatitis C virus
• Subjects with active ethanol abuse, as judged by the investigator
• Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
• Female subject is not willing to use highly effective contraception during treatment and for at least 1 month after the end of treatment
• Female subject is pregnant or planning to become pregnant within 1 month after the end of treatment
• Subject has known sensitivity to any of the products to be administered during dosing
• Subject has previously been randomised into this study
• Subject will not be available for protocol-required study visits, to the best of the subject and investigator's knowledge
• Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
• Confirmed history of neutralising antibody activity to rHuEpo or darbepoetin alfa

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Innsbruck, , Austria

Research Site

Linz, , Austria

Research Site

Salzburg, , Austria

Research Site

Vienna, , Austria

Research Site

Bruges, , Belgium

Research Site

Brussels, , Belgium

Research Site

Charleroi, , Belgium

Research Site

Ghent, , Belgium

Research Site

Haine Saint Paul - La Louviere, , Belgium

Research Site

Hasselt, , Belgium

Research Site

Leuven, , Belgium

Research Site

Liège, , Belgium

Research Site

Ottignies, , Belgium

Research Site

Roeselare, , Belgium

Research Site

Sint-Niklaas, , Belgium

Research Site

Brno, , Czechia

Research Site

Hradec Králové, , Czechia

Research Site

Olomouc, , Czechia

Research Site

Ostrava-Poruba, , Czechia

Research Site

Prague, , Czechia

Research Site

Prague, , Czechia

Research Site

Prague, , Czechia

Research Site

Prague, , Czechia

Research Site

Zlín, , Czechia

Research Site

Avignon, , France

Research Site

Bobigny, , France

Research Site

Caen, , France

Research Site

Lyon, , France

Research Site

Lyon Cédex 3, , France

Research Site

Nantes, , France

Research Site

Nice, , France

Research Site

Paris, , France

Research Site

Paris, , France

Research Site

Pontoise, , France

Research Site

Toulouse, , France

Research Site

Vandœuvre-lès-Nancy, , France

Research Site

Cologne, , Germany

Research Site

Dresden, , Germany

Research Site

Göttingen, , Germany

Research Site

Hanover, , Germany

Research Site

Leipzig, , Germany

Research Site

Mannheim, , Germany

Research Site

Regensburg, , Germany

Research Site

Rotenburg (Wümme), , Germany

Research Site

Ulm, , Germany

Research Site

Athens, , Greece

Research Site

Athens, , Greece

Research Site

Ioannina, , Greece

Research Site

Pátrai, , Greece

Research Site

Thessaloniki, , Greece

Research Site

Alessandria, , Italy

Research Site

Bologna, , Italy

Research Site

Genova, , Italy

Research Site

Milan, , Italy

Research Site

Palermo, , Italy

Research Site

Pavia, , Italy

Research Site

Pesaro, , Italy

Research Site

Pisa, , Italy

Research Site

Reggio Calabria, , Italy

Research Site

Rionero in Vulture PZ, , Italy

Research Site

Roma, , Italy

Research Site

San Giovanni Rotondo FG, , Italy

Research Site

Udine, , Italy

Research Site

Zaragoza, Aragon, Spain

Research Site

Salamanca, Castille and León, Spain

Research Site

Barcelona, Catalonia, Spain

Research Site

Valencia, Valencia, Spain

Research Site

Valencia, Valencia, Spain

Research Site

Basel, , Switzerland

Research Site

Lucerne, , Switzerland

Research Site

Muensterlingen, , Switzerland

Research Site

Zurich, , Switzerland

Countries

Austria; Belgium; Czechia; France; Germany; Greece; Italy; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 28626220 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2009-016522-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20090160

Identifier Type: -

Identifier Source: org_study_id