Condition category
Cancer
Date applied
13/06/2016
Date assigned
20/06/2016
Last edited
22/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Mrs Sonia Fox

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
Institute of Cancer and Genomics
Vincent Drive
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2015-005497-38

ClinicalTrials.gov number

Protocol/serial number

30849

Study information

Scientific title

Effects of TAMoxifen on the Mutant Allele Burden and Disease Course in Patients with MyeloprolifeRatIve Neoplasms

Acronym

TAMARIN

Study hypothesis

The aim of this study is to assess whether giving tamoxifen to patients receiving therapy for their MPN reduces the number of mutated cells found in the blood by ≥ 50% after 24 weeks of treatment compared to the start of the study.

Ethics approval

East Midlands – Derby Research Ethics Committee, 24/05/2016, ref: 16/EM/0181

Study design

Non-randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Haematological oncology; UKCRC code/ Disease: Cancer/ Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue

Intervention

Patients who consent to participate in the study will need to attend hospital at baseline to receive a medical exam (including palpation of the liver and spleen), blood tests (including a full fasting lipid profile), an abdominal ultrasound if they have PV or ET and a blood sample taken for central review at Cambridge Blood and Stem Cell Biobank to ensure that they are eligible for the trial and that it is safe for them to enter the trial. Patients will also be asked to complete a short Quality of Life questionnaire which has been developed specifically for patients with MPNs.

Once registered to the study, patients will have a minimum of 24 weeks of treatment with tamoxifen at 20mg od as an oral tablet.
Patients will be seen 2 weeks after starting treatment for blood tests and a medical exam and then again at weeks 4, 8, 12, 18 and 24. At weeks 12 and 24 they will also have a blood sample taken for central review at Cambridge and a full fasting lipid profile. At week 24, the patient will also be asked to have a bone marrow aspirate and trephine biopsy and complete the same Quality of Life Questionnaire they completed at baseline. If the patient had an enlarged spleen on the baseline ultrasound, an ultrasound may be repeated at any point during the 24 weeks if the blood counts suggest the patient is in Complete Response.

If the patient continues trial therapy beyond 24 weeks, they will be seen a minimum of 12 weekly for blood tests and a medical exam.
Patients will also be required to attend their local hospital 28 days after the final dose of tamoxifen for blood tests and a medical exam.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Peripheral blood JAK2V617F or CALR mutant allele burden is measured using validated assays for JAK2V617F and CALR respectively at baseline and 24 weeks.

Secondary outcome measures

1. Peripheral blood JAK2V617F or CALR mutant allele burden is measured using validated assays for JAK2V617F and CALR respectively at baseline and 12 weeks
2. Peripheral blood JAK2V617F or CALR mutant allele burden is measured using validated assays for JAK2V617F and CALR respectively at baseline and 24 weeks
3. Peripheral blood JAK2V617F or CALR mutant allele burden is measured using validated assays for JAK2V617F and CALR respectively at baseline and 12 weeks
4. Toxicity measured as the number of grade 3 and 4 adverse events reported according to CTCAE for the duration of treatment (and including 4 weeks after the last administration of trial treatment).
5. Thrombotic events of any grade reported according to CTCAE for the duration of treatment (and including 4 weeks after the last administration of trial treatment)
6. Duration of haematological response calculated as time from registration to loss of response for PV/ET patients or evidence of disease progression for MF patients. PV/ET patients who continue to achieve a response, or MF patients who have no evidence of disease progression at the end of the trial will be censored at date last seen
7. Response according to IWG-MRT response criteria for MF and 2013 ELN response for ET/PV measured at 24 weeks

Overall trial start date

25/11/2015

Overall trial end date

31/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age ≥ 60 years (men aged between 50-59 may also be considered following discussion with the Chief Investigator)
2. Women must be post-menopausal (defined as amenorrhoeic for at least 12 consecutive months following cessation of all exogenous hormonal treatments)
3. Confirmed diagnosis of JAK2-V617F or CALR positive Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Myelofibrosis (MF) (primary or secondary) for ≥ 6 months
•4. JAK2-V617F or CALR mutant allele burden ≥ 20% in peripheral blood granulocyte DNA at study entry (assessed via central review)
5. WHO performance status 0-2
6. For patients with PV or ET, maintenance of at least a partial haematological response according to 2009 ELN criteria must have been achieved for the previous 6 months (prior to registration), without introduction of any new therapeutic agents for their MPN
7. 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.
8. Patients receiving cytoreductive therapy for their MPN (not solely aspirin or venesection)
9. Adequate hepatic function, defined as:
9.1. bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
9.2. AST/ALT/ALP ≤ 2.5 x ULN
10. Adequate renal function (creatinine clearance > 30 mL/min)
11. Male patients must agree to use effective contraception during participation in the trial and for 2 months after the last dose of trial treatment
12. 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%”

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 42; UK Sample Size: 42

Participant exclusion criteria

1. Leukaemic transformation ( > 20% blasts in blood, marrow or extramedullary site).
2. Accelerated phase of disease as indicated by > 5% blasts in the peripheral blood
3. Treatment of ET, PV or MF with Interferon alpha or JAK inhibitors, such as ruxolitinib, or other investigational agents for their MPN within 6 months prior to trial entry
4. Any of the following previous thrombotic events at any time:
4.1. Portal or other splanchnic venous thrombosis
4.2. Vascular access complication
4.3. Ischemia cerebrovascular
4.4. Stroke
4.5. Transient Ischaemic attack
4.6. Superficial thrombophlebitis
4.7. Venous Thromboembolic events including pulmonary embolism (PE) and deep vein thrombosis (DVT)
4.8. Peripheral vascular ischemia
4.9. Visceral arterial ischemia
4.10. Acute coronary syndrome
4.11. Myocardial infarction
5. Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
6. Previous endometrial cancer, hyperplasia or polyps
7. Prior treatment with hematopoietic stem cell transplantation
8. Patients who do not carry any mutations in JAK2V617F or CALR or allele burden < 20%
9. Female patients receiving hormone replacement therapy
10. Hypertriglyceridemia > grade 1
11. 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)
12. Known hypersensitivity to tamoxifen or hypersensitivity to any other component of tamoxifen
13. Concomitant drugs contraindicated for use with the trial drug according to the Summary of Product Characteristics
14. Known planned scheduled elective surgery during study with the exception of dental and low risk eye surgery (e.g. cataracts)

Recruitment start date

01/08/2016

Recruitment end date

31/07/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
Institute of Cancer and Genomics Vincent Drive University of Birmingham Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Leukaemia and Lymphoma Research

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results of this trial will be submitted for publication in a peer reviewed journal.

Intention to publish date

01/05/2018

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

22/09/2016: Cancer Help lay summary added.