Darbepoetin Alfa in Anemic Low or Intermediate-1 Risk MDS Subjects
Information source: Amgen
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: MDS
Intervention: Darbepoetin alfa (Drug); Placebo (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Amgen Official(s) and/or principal investigator(s): MD, Study Director, Affiliation: Amgen
Summary
This is a Phase 3, multicenter, randomised, double-blind, placebo-controlled trial of
darbepoetin alfa 500 μg administered once every 3 weeks (Q3W) to approximately 141 low or
intermediate-1 risk anaemic MDS subjects who have not previously received
erythropoiesis-stimulating agents (ESAs) or biologic response modifiers to treat MDS. 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 subjects 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 Q3W (2 weeks after the last dose of darbepoetin alfa
administered every 2 weeks [Q2W]) for subjects who withdraw from the study.
Long-term follow-up (LTFU) will occur every 26 weeks (± 4 weeks) from the EOATP visit (or
EOTP visit if the subject 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 subject's survival and progression to AML status will
be collected during LTFU.
Approximately 141 subjects who meet all eligibility requirements will be randomised in a 2: 1
ratio to 1 of 2 groups:
1. darbepoetin alfa 500 μg Q3W (n=94)
2. placebo Q3W (n=47)
Randomisation will be stratified by the International Prognostic Scoring System (IPSS)
category (low versus intermediate-1) established at screening.
Clinical Details
Official title: A Multicenter, Randomised, Double-blind, Placebo-controlled Study of Darbepoetin Alfa for the Treatment of Anaemic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care
Primary outcome: To assess the superiority of darbepoetin alfa versus placebo on the incidence of RBC transfusions during the double-blind treatment period.
Secondary outcome: Adverse events, including treatment-emergent adverse events of interest (eg, pure red cell aplasia [PRCA]; thrombovascular events (TVE) [arterial thrombovascular events (ATE) and venous thrombovascular events (VTE)])Mortality through EOTP, EOATP, and LTFU Disease progression to acute myeloid leukemia (AML) through EOTP, EOATP, and LTFU Proportion of subjects acheiving International Working Group (IWG) erythroid response during the double-blind treatment period. Attaining a clinically meaningful change from baseline to EOTP in FACIT-F: improvement (at least a 3-point increase), deterioration (at least a 3-point decrease), unchanged (less than a 3-point in either direction) Change in patient-reported fatigue and overall health status from baseline to week 13, EOTP, week 31, week 42/43, week 54/55, and week 72/73/ EOATP as measured by the Functional Assessment of Chronic Illness Therapy (FACIT-F) & EuroQOL-5D Malignancies other than AML, basal cell carcinoma, or squamous cell carcinoma of the skin through EOTP Neutralising antibody formation to darbepoetin alfa
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Low or intermediate-1 risk MDS patients per 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 centralised review at any
time throughout the study
- World Health Organization (WHO) classification of refractory anaemia (RA), refractory
anaemia 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 International
Prognostic Scoring System (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 ESA therapy, eg, 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 G-CSF therapy within 30 days prior to randomisation 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
Locations and Contacts
Research Site, Innsbruck 6020, Austria
Research Site, Linz 4020, Austria
Research Site, Salzburg 5020, Austria
Research Site, Wien 1140, Austria
Research Site, Brugge 8000, Belgium
Research Site, Bruxelles 1200, Belgium
Research Site, Charleroi 6000, Belgium
Research Site, Gent 9000, Belgium
Research Site, Haine St. Paul - La Louviere 7100, Belgium
Research Site, Hasselt 3500, Belgium
Research Site, Leuven 3000, Belgium
Research Site, Liege 4000, Belgium
Research Site, Ottignies 1340, Belgium
Research Site, Roeselare 8800, Belgium
Research Site, Sint-Niklaas 9100, Belgium
Research Site, Brno 625 00, Czech Republic
Research Site, Hradec Kralove 500 05, Czech Republic
Research Site, Olomouc 775 20, Czech Republic
Research Site, Ostrava-Poruba 708 52, Czech Republic
Research Site, Praha 10 100 34, Czech Republic
Research Site, Praha 2 128 08, Czech Republic
Research Site, Praha 2 128 20, Czech Republic
Research Site, Praha 5 150 06, Czech Republic
Research Site, Zlin 760 01, Czech Republic
Research Site, Avignon Cedex 9 84902, France
Research Site, Bobigny cedex 93009, France
Research Site, Caen 14033, France
Research Site, Lyon Cédex 3 69437, France
Research Site, Lyon 69009, France
Research Site, Nantes Cedex 1 44035, France
Research Site, Nice Cedex 3 06202, France
Research Site, Paris Cedex 10 75475, France
Research Site, Paris 75015, France
Research Site, Pontoise Cedex 95301, France
Research Site, Toulouse Cedex 9 31059, France
Research Site, Vandoeuvre les Nancy 54511, France
Research Site, Dresden 01307, Germany
Research Site, Göttingen 37075, Germany
Research Site, Hannover 30625, Germany
Research Site, Köln 50677, Germany
Research Site, Leipzig 04103, Germany
Research Site, Mannheim 68167, Germany
Research Site, Regensburg 93053, Germany
Research Site, Rotenburg (Wümme) 27356, Germany
Research Site, Ulm 89081, Germany
Research Site, Athens 11527, Greece
Research Site, Athens 12462, Greece
Research Site, Ioannina 45110, Greece
Research Site, Patra 26500, Greece
Research Site, Thessaloniki 57010, Greece
Research Site, Alessandria 15100, Italy
Research Site, Bologna 40138, Italy
Research Site, Genova 16132, Italy
Research Site, Milano 20122, Italy
Research Site, Palermo 90146, Italy
Research Site, Pavia 27100, Italy
Research Site, Pesaro 61100, Italy
Research Site, Pisa 56127, Italy
Research Site, Reggio Calabria 89124, Italy
Research Site, Rionero in Vulture PZ 85028, Italy
Research Site, Roma 00161, Italy
Research Site, San Giovanni Rotondo FG 71013, Italy
Research Site, Udine 33100, Italy
Research Site, Basel 4031, Switzerland
Research Site, Luzern 6000, Switzerland
Research Site, Muensterlingen 8596, Switzerland
Research Site, Zurich 8091, Switzerland
Research Site, Zaragoza, Aragón 50009, Spain
Research Site, Salamanca, Castilla León 37007, Spain
Research Site, Barcelona, Cataluña 08003, Spain
Research Site, Valencia, Comunidad Valenciana 46010, Spain
Research Site, Valencia, Comunidad Valenciana 46026, Spain
Additional Information
AmgenTrials clinical trials website
Starting date: December 2011
Last updated: August 10, 2015
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