The effects of Tamoxifen on the disease course of patients with Myeloproliferative Neoplasms

Phase 1

• Conditions: Myeloproliferative Neoplasms; MedDRA version: 20.0Level: LLTClassification code 10028576Term: Myeloproliferative disorderSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005497-38-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-28
• Last Update Posted: 29 May 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age = 60 years (men aged between 50-59 may also be considered following discussion with the Chief Investigator)
• Women must be post-menopausal (defined as amenorrhoeic for at least 12 consecutive months following cessation of all exogenous hormonal treatments)
• Confirmed diagnosis of JAK2-V617F or CALR 5bp insertion (exon 9) or CALR 52bp deletion (exon 9) positive Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Myelofibrosis (MF) (primary or secondary) for = 6 months
• JAK2-V617F or CALR 5bp insertion (exon 9) or CALR 52bp deletion (exon 9)mutant allele burden = 20% in peripheral blood granulocyte DNA at study entry (assessed via central review)
• WHO performance status 0-2
• For patients with PV or ET, maintenance of platelet count =600 x 10^9/L, WBC =25 x 10^9/L and venesection requirements =1 per month for the previous 3 months (prior to registration), without introduction of any new therapeutic agents for their MPN for 6 months prior to registration
• For patients with MF, there must not have been any evidence of disease progression* for the previous 6 months (prior to registration) and no new therapeutic agents for their MPN introduced during this period.
• Patients receiving cytoreductive therapy (with the exception of interferon alpha or investigational agents) for their MPN (not solely aspirin or venesection)
• Adequate hepatic function, defined as:
o bilirubin = 1.5 x upper limit of normal (ULN) (patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
o AST/ALT/ALP = 2.5 x ULN
• Adequate renal function (creatinine clearance >30 mL/min)
• Male patients must agree to use effective contraception during participation in the trial and for 2 months after the last dose of trial treatment
• Patient must be able to give written informed consent
*Defined by IWG-MRT ELN criteria (Appendix 6). Please note no baseline bone marrow is required to confirm absence of Leukemic transformation confirmed by a bone marrow blast count of =20%”.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

• Leukaemic transformation (>20% blasts in blood, marrow or extramedullary site).
• Accelerated phase of disease as indicated by >10% blasts in the peripheral blood
• Treatment of ET, PV or MF with Interferon alpha or other investigational agents for their MPN within 6 months prior to trial entry. JAK inhibitors, such as ruxolitinib, are allowed if taken continuously for =6 months prior to registration (dose changes during that period will be allowed)
• Any of the following previous thrombotic events at any time:
o Portal or other splanchnic venous thrombosis
o Vascular access complication
o Ischemia cerebrovascular
o Stroke
o Transient Ischaemic attack
o Superficial thrombophlebitis
o Venous Thromboembolic events including pulmonary embolism (PE) and deep vein thrombosis (DVT)
o Peripheral vascular ischemia
o Visceral arterial ischemia
o Acute coronary syndrome
o Myocardial infarction
• Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
• Previous endometrial cancer, hyperplasia or polyps
• Prior treatment with hematopoietic stem cell transplantation
• Patients who do not carry JAK2V617F, CALR 5bp insertion (exon 9) or CALR 52bp deletion (exon 9) mutations, or whose allele burden is <20% at study entry
• Female patients receiving hormone replacement therapy
• Hypertriglyceridemia > grade 1
• Any serious underlying medical condition (at the judgment of the Investigator), which could impair the ability of the patient to participate in the trial (e.g. liver disease, active autoimmune disease, uncontrolled diabetes, uncontrolled infection (HIV, Hepatitis B and C), known genetic defect (apart from MPN) relating to venous thromboembolic events, or psychiatric disorder precluding understanding of trial information)
• Known hypersensitivity to tamoxifen or hypersensitivity to any other component of tamoxifen
• Concomitant drugs contraindicated for use with the trial drug according to the Summary of Product Characteristics
• Known planned scheduled elective surgery during study with the exception of dental and low risk eye surgery (e.g. cataracts)

Study & Design

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