Safety and efficacy study for comparison of two different anagrelide formulations in patients with Essential Thrombocythemia

• Conditions: male or femal patients with confirmed diagnosis of Essential Thrombocythemia; MedDRA version: 17.0Level: LLTClassification code 10015494Term: Essential thrombocythemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-003410-41-LT
• Lead Sponsor: AOP Orphan Pharmaceuticals AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-18
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Willing and able to give written informed consent prior to any study specific procedures and able to comply with this protocol.

• Male / female

• Age =18 years

• Confirmed diagnosis of ET according to 2008 World Health Organization (WHO) diagnostic criteria*, defined as meeting all four criteria as follows:

a. Sustained platelet count =450 G/L.
b. Bone marrow biopsy specimen showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes. No significant increase or left shift of neutrophil granulopoiesis or erythropoiesis. (Bone marrow examination should be available as source data and based on existing biopsies – no screening assessment.)
c. Not meeting WHO criteria for polycythemia vera, primary myelofibrosis, BCR-ABL1-positive chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm.
d. Demonstration of JAK2V617F or other clonal marker, or in the absence of JAK2V617F, no evidence for reactive thrombocytosis.

* If the diagnosis was made according to earlier criteria (for example, Polycythemia Vera Study Group [PVSG]), re-examination and confirmation of diagnosis according to 2008 WHO criteria must be done. In the source data a notice by investigator should be made: ‘Reclassified according to WHO 2008 criteria for ET’.

AND:
• at high risk of experiencing ET-related events, indicated for Thromboreductin® treatment as defined by one or more of the following criteria:

o Age = 60 years
o Platelet counts = 1000 G/L
o Increase of platelet count = 300 G/L within 3 months
o Severe thrombohemorrhagic or ischemic symptoms in anamnesis

EITHER:
• Currently treated with anagrelide (Thromboreductin® or other locally available anagrelide formulations), meeting the definition of well controlled disease. Well controlled disease is defined as the absence at screening of any acute disease related symptoms, as well as the achievement of stable platelet counts (<600 G/L AND fluctuation of these values of not more than +/- 30 %, confirmed at the Screening Visit and one previous measurement within 3 months before Screening).

OR:
• Naive:
a. ET treatment naive: no cytoreductive treatment received yet
b. Anagrelide naive, defined as meeting ALL of the below mentioned criteria:
o Treatment received has to be another cytoreductive treatment than anagrelide (e.g. Hydroxyurea, Busulfan, Interferons).
o This cytoreductive treatment had to be terminated either due to intolerance or lack of reduction of the elevated platelet counts. Intolerance to hydroxyurea is defined according to LeukemiaNet European Collaboration (see Appendix 5). Intolerance to busulfan, interferon (IFN) or another cytoreductive treatment than anagrelide is defined as any NCI CTCAE 4.0 toxicity of = grade 2 (see Appendix 7).
o Termination of treatment has to be at least four weeks before start of study medication/randomization.

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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 67

Exclusion Criteria

• Diagnosis of any other myeloproliferative disorder

• Any known cause for a secondary thrombocytosis, e.g. thrombocytosis due to iron deficiency

• ET currently well controlled by another cytoreductive treatment than Anagrelide (e.g. hydroxyurea, busulfan, IFN) AND the opportunity to continue to receive this treatment

• ET currently treated with combination of any two of the following agents: anagrelide, hydroxyurea, interferons, busulfan

• Hypersensitivity to either active or non-active ingredients of anagrelide or to any other excipients of the investigational products

• Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

• Cardiovascular disease grade 3 with a negative benefit/risk assessment or grade 4 (South West Oncology Group, see Appendix 6)

• Clinically significant abnormal laboratory values (excluding markers for ET) in investigator’s opinion, including electrolyte imbalance

• Severe renal insufficiency (creatinine clearance <30 ml/min)

• Moderate to severe hepatic insufficiency (ALT or AST > 5 times upper normal limit [UNL])

• White blood count (WBC) = 15 G/L at screening

• Diagnosis of any malignancy, other than ET (except basal cell and squamous cell carcinomas of the skin and carcinoma in situ of the cervix that have been completely excised and are considered cured), within the last 3 years, or coexisting, malignant, systemic disease

• Poorly controlled diabetes mellitus

• Known infection with hepatitis B, hepatitis C or HIV

• Pregnant or lactating women (pregnancy test to be performed within 7 days prior study treatment start)

• Women of childbearing potential or male patients, who have sexual intercourse with females of childbearing potential, not willing to use an effective method of contraception during the study. Effective methods for women are hormonal contraceptives, intrauterine devices (IUDs), surgical intervention, and sexual abstinence. Female patients with childbearing potential receiving oral hormonal contraception will have to apply an additional effective method of contraception during the study period. Effective methods for men are condoms and sexual abstinence.

• History of drug/alcohol abuse within the previous 2 years

• Participation in another investigational study within 4 weeks prior to informed consent signed or for a longer duration if specified in local regulations

• Any significant psychiatric disorder that, in the opinion of the investigator, might prohibit the understanding and giving of informed consent, or that might prevent the patient from completing the trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified