An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000144-92-SE
• Date of registration: 28/04/2006
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
• Scientific title: An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
• Date of first enrolment: 07/06/2006
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000144-92
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: sequential cohort dose escalation study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Netherlands, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Diagnosis of MDS using the World Health Organization classification
Low or intermediate-1 risk MDS using the IPSS
The mean of the two platelet counts taken within 1 week prior to dosing must be =50 x 109/L, with no individual count >55 x 109/L (5 patients enrolled at the MTD must be =20 x 109/L). Standrad of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1.
Subjects must be 18 years of age at the time of obtaining informed consent
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Adequate Liver Function, as evidenced by a serum bilirubin =1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert’s Disease), ALT = 3 times the laboratory normal range, and AST = 3 times the laboratory normal range
A serum creatinine concentration = 2 mg/dl (=176.8 mmol/L)
Written Informed Consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Currently receiving any treatment for MDS other than transfusions and erythropoeitic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1.
Clinically significant bleeding within 2 weeks prior to screening ( eg, GI bleeds, intracranial hemorrhage) .
Prior malignancy ( other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for = 3 years before screening.
Prior history of bone marrow transplantation.
Persistent peripheral blood monocytosis (> 3 months with an absolute monocyte count > 1,000/pL).
Unstable angina, congestive heart failure [NYHA > class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction.
Received Anti-Thymocyte Globuline (ATG) within 6 months of screening.
Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening.
Received IL-11 (oprelvekin) within 4 weeks before screening.
Concurrent use of granulocyte growth factors (i.e. G-CSF(Neupogen°, Granocyte°), pegfilgrastim (Neulasta°), GM-CSF (Leukine, Prokine, Sargramostim)).
Have ever previously received rTPO, PEG-rHuMGDF, eltrombopag, or AMG 531.
Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication.
Other investigational procedures are excluded.
History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year.
History of venous thrombosis that currently requires anti- coagulation therapy. Untreated B12 or folate deficiency.
Subject is evidently pregnant (eg, positive HCG test) or is breast feeding.
Subject is not using adequate contraceptive precautions.
Subject has known hypersensitivity to any recombinant E coli- derived product.
Subject previously has enrolled in this study.
Subject will not be available for follow- up assessment.
Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
MedDRA version: 9.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome

Intervention(s)

Product Name: recombinant megakaryopoeisis-stimulating protein
Product Code: AMG 531
Pharmaceutical Form: Powder and solvent for solution for injection
Current Sponsor code: AMG 531
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 600-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of AMG 531 in thrombocytopenic subjects with low or Intermediate-1 risk MDS.

Primary end point(s): The primary endpoint is the incidence and severity of all adverse events and evaluation of antibody status. The MTD of AMG 531 in thrombocytopenic subjects with low or intermediate-1 risk MDS will be identified based on safety data. The MTD is defined as the dose where < 34% of subjects experience a related grade 3-4 toxicity. The key secondary endpoint is the proportion of subjects achieving a complete or major platelet response (platelet response defined by a modified MDS International Working Group Classification).

Secondary Objective: Part A:

To evaluate the platelet response of thrombocytopenic subjects with low or intermediate-1 risk MDS receiving AMG 531.

Part B:

Part B: To assess the pharmacodynamics (PD) and pharmacokinetics (PK) of three dosing schedules of AMG 531 administered via subcutaneous or intravenous administration in thrombocytopenic subjects with MDS.

Secondary ID(s)

20050159

2006-000144-92-GB