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Report for Clinical Trial NCT04116502

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase III, Randomised, Open-label, Multicenter International Trial Comparing Ruxolitinib With Either HydRoxycarbamIDe or Interferon Alpha as First Line ThErapy for High Risk Polycythemia Vera

The trial will be a phase III, randomised-controlled, multi-centre, international, open-label trial consisting of ruxolitinib versus best available therapy, where best available therapy is a choice of interferon alpha, any formulation permitted (IFN) or hydroxycarbamide (HC), and which will be elected by the Investigator prior to randomisation.

NCT04116502 Polycythemia Vera
MeSH:Polycythemia Vera Polycythemia
HPO:Polycythemia

3 Interventions

Name: Ruxolitinib

Description: 10mg of ruxolitinib twice daily (bd)
Type: Drug
Group Labels: 1

A- Ruxolitinib

Name: Hydroxycarbamide

Description: Via standard hospital mechanisms
Type: Drug
Group Labels: 1

B- Hydroxycarbamide OR Interferon A

Name: Interferon-Alpha

Description: Any formulation, via standard hospital mechanisms
Type: Drug
Group Labels: 1

B- Hydroxycarbamide OR Interferon A


Primary Outcomes

Description: Event Free Survival

Measure: Event Free Survival (EFS)

Time: the time from randomisation to the date of the first major thrombosis/haemorrhage, death,transformation to Myelodisplastic Syndromes, Acute Myeloid Leukaemia or Post-polycythemia Vera Myelofibrosis, if within the ~3 year trial period

Secondary Outcomes

Description: As defined in the protocol, combined and split to venous and arterial

Measure: Major thrombosis

Time: Occuring while on treatment (over 3 years)

Description: As defined in the protocol

Measure: Major haemorrhage

Time: Occuring while on treatment (over 3 years)

Description: Transformation to PPV-MF

Measure: Transformation to PPV-MF

Time: Occuring while on treatment (over 3 years)

Description: Transformation to MDS and/or AML

Measure: Transformation to MDS and/or AML

Time: Occuring while on treatment (over 3 years)

Description: As defined by ELN response criteria at 1 year

Measure: Complete Haematological remission (CHR)

Time: 1 year post-treatment

Description: As measured via MPN-SAF

Measure: Symptom burden/Quality of life (MPN-SAF)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: As measured via MDASI

Measure: Symptom burden/Quality of life (MDASI)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: As measured via EQ-5D

Measure: Symptom burden/Quality of life (EQ-5D)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: Including cost utility and cost effectiveness analyses as defined by the protocol (e.g. QALYs)

Measure: Health economics

Time: At the end of the trial (trial duration of approximately 8 years)

Description: According to ELN response criteria

Measure: Peripheral blood JAK2 V617F allele burden

Time: At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation)

Description: Trial discontinuation

Measure: Rates of discontinuation

Time: From treatment prior to protocol defined 3 years

Description: collected according to CTCAE version 4.0 and the MITHRIDATE protocol

Measure: Rate and severity of adverse events

Time: Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation))

Description: in patients with splenomegaly

Measure: Spleen response

Time: Response at 1 year post randomisation

Description: Time free from venesection

Measure: Time free from venesection

Time: Defined as the mean time between venesections while on trial treatment (treatment duration of 3 years)

Description: Malignancy independent to the original diagnosis

Measure: Secondary malignancy

Time: Occuring throughout the trial (from randomisation until approximately 3 years post-randomisation)

Description: Change in QRisk score

Measure: Change in QRisk score

Time: Collected at baseline and years 1, 2 and 3

Other Outcomes

Description: Progression of marrow fibrosis (bone marrow collected and analysed at the Weatherall Institute of Molecular Medicine (WIMM) in Oxford

Measure: Progression of marrow fibrosis

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Impact of treatment on molecular signatures of disease (as analysed by the WIMM in Oxford)

Measure: Impact of treatment on molecular signatures of disease

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: within the stem/progenitor cell compartment (as analysed by the WIMM in Oxford)

Measure: Clonal involvement

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: (acquisition of additional mutations, as analysed by the WIMM in Oxford)

Measure: Clonal evolution

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: of other disease-association mutations (as analysed by the WIMM in Oxford)

Measure: Reduction of peripheral blood allele burden

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: and any change over time (as analysed by the WIMM in Oxford)

Measure: Assessment of the prevalence of clonality markers for haematological disease

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: (angina, acute coronary syndrome, acute MI; arrhythmia)

Measure: Cardiac event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Pulmonary hypertension as assessed clinically

Measure: Pulmonary hypertension

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: e.g. angiogram, angioplasty, CABG

Measure: Coronary intervention

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: e.g. LVEF% on ECHO/MUGA and/or NYHA classification

Measure: Deterioration in cardiac function

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: TIA, haemorrhagic CVA, non-haemorrhagic CVA

Measure: Cerebrovascular event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: peripheral vascular disease: claudication, carotid stenosis

Measure: Arterial vascular event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: including DVT, PE, Cerebral, splanchnic, other

Measure: Venous thrombosis

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Pregnancy loss

Measure: Pregnancy loss

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V617F

Peripheral blood JAK2 V617F allele burden. --- V617F ---

Symptom burden/(QALY)quality of life years gained 7. Health economics including cost utility and cost effectiveness analyses 8. Peripheral blood JAK2 V617F allele burden according to ELN response criteria 9. Rates of discontinuation 10. --- V617F ---



HPO Nodes


HPO: