Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Myeloproliferative Disorders

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Participants will receive bomedemstat daily for 169 days with additional treatment continuing in participants deriving clinical benefit.

Bomedemstat

Medical Director

This is a multi-center, open-label extension study to assess the long-term safety and efficacy of bomedemstat (MK-3543, formerly called IMG-7289) administered orally once daily in participants with an MPN who participated in a prior bomedemstat study such as, but not limited to, IMG-7289-CTP-102 and IMG-7289-CTP-201 (referred to hereafter as 'feeder studies').

Extension Study of Bomedemstat (IMG-7289/MK-3543) in Participants With Myeloproliferative Neoplasms (IMG-7289-CTP-202/MK-3543-005)

A Multi-Center, Open Label, Extension Study Evaluating the Safety and Efficacy of Bomedemstat for the Treatment of Patients With Myeloproliferative Neoplasms (MPNs) Enrolled in a Prior Bomedemstat Clinical Study

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

The MPN-SAF is a questionnaire to assess symptoms including fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Participant responses for each symptom is scored on an 11-point scale (0 = absent/as good as it can be to 10 = worst imaginable/as bad as it can be). The MPN-SAF TSS is the summation of all the individual scores on a 100-point scale. The participant-reported symptom burden response rate will be assessed as the change from baseline in the percentage of participants who achieve a ≥50% reduction to the MPN-SAF TSS.

ORR is the percentage of participants with Complete Response (CR) or Partial Response (PR) per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) response criteria. For MF participants, CR is, in bone marrow: age-adjusted normocellularity, \<5% blasts; ≤grade 1 MF AND hemoglobin (Hb) ≥100 g/L and \<upper normal limit (UNL); neutrophil count ≥ 1 x 10\^9/L and \<UNL; platelet count ≥100 x 10\^9/L and \<UNL; \<2% immature myeloid cells AND resolution of disease symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis. For MF participants, PR is all CR criteria WITH Hb ≥85 but \<100 g/L and platelet count ≥50, but \<100 x 10\^9/L and \<UNL OR WITHOUT bone marrow criteria.

For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented progressive disease (PD) or death. For MF participants, PD is the appearance of a new splenomegaly that is palpable at least 5 cm below the left costal margin (LCM) OR a ≥100% increase in palpable distance, below LCM, for baseline splenomegaly of 5-10 cm OR a 50% increase in palpable distance, below LCM, for baseline splenomegaly of \>10 cm OR leukemic transformation confirmed by a bone marrow blast count of ≥20% OR a peripheral blood blast content of ≥20% associated with an absolute blast count of ≥1 x 109/L that lasts for at least 2 weeks.

ORR is the percentage of participants with CR or PR per IWG-MRT and ELN response criteria. For ET participants, CR is durable resolution of disease-related signs, AND platelet count ≤400 x 10\^9/L, WBC count \<10 x 10\^9/L, absence of leukoerythroblastosis, AND without signs of progressive disease, and absence of any hemorrhagic or thrombotic events, AND bone marrow histological remission. For ET participants, PR is all CR criteria WITHOUT bone marrow histological remission.

For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented PD or death. For ET participants, PD is transformation into PV, post-ET myelofibrosis, myelodysplastic syndrome, or acute leukemia.

Spleen size will be measured by palpation at pre-specified timepoints. The change from baseline in spleen size will be presented.

Mutant (variant) allele burden will be assessed by genetic testing of germline samples, peripheral blood, and bone marrow at pre-specified timepoints. The change from baseline in the mutant allele burden will be presented.

CBC will include red and white blood cell (RBC and WBC) and circulating blast cell counts. Blood samples will be taken at pre-specified timepoints to determine CBC. The change from baseline in CBC will be presented.

The PGIC is a single-score questionnaire and is scored on a scale of 1 to 7. A higher score indicates a worse outcome. The changes from baseline in the PGIC score will be reported.

The number of participants who experience a thrombotic or hemorrhagic event will be reported

An AE is any undesirable physical, psychological or behavioral effect experienced by a patient during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any untoward signs or symptoms experienced by the patient from the time of first dose with bomedemstat under this protocol until completion of the study.

An SAE is defined as any AE, whether or not related to the study drug, which results in the following outcomes:

* Death
* Life-threatening experience
* Required or prolonged inpatient hospitalization
* Persistent or significant disability/incapacity
* Congenital anomaly
* Important medical events that, based upon appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.

Vital signs will include resting heart rate, semi-supine systolic/diastolic blood pressure, respiratory rate and body temperature. Clinical significance will be determined by the investigator.

Laboratory investigation will include hematology, coagulation, clinical chemistry and urinalysis. Clinical significance will be determined by the investigator.

Spleen volume will be assessed by magnetic resonance imaging (MRI) (or computed tomography \[CT\] where applicable) at pre-specified timepoints. Change from baseline in spleen volume will be reported.

Blood samples will be collected at pre-specified timepoints to determine platelet counts. Change from baseline in platelet counts will be reported.

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Neoplasms

Polycythemia Vera

Polycythemia

Bone Marrow Neoplasms

Hematologic Neoplasms

gelatin capsules supplied in 5-mg, 25-mg, and 100-mg strengths

XL019

The purpose of this study is to evaluate the safety and tolerability of XL019 in adults with myelofibrosis. XL019 is a selective inhibitor of the cytoplasmic tyrosine kinase JAK2. JAK2 is activated by cytokine and growth factor receptors and phosphorylates members of the STAT family of inducible transcription factors. Activation of the JAK/STAT pathway promotes cell growth and survival, and is a common feature of human tumors. JAK2 is activated by mutation in the majority of patients with myelofibrosis, polycythemia vera and essential thrombocytosis and appears to drive the inappropriate growth of blood cells in these conditions.

A Safety Study of XL019 in Adults With Myelofibrosis

A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL019 Administered to Subjects With Myelofibrosis

Exelixis

Chunyan Song, MD/Senior Manager, Clinical Research

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Wounds and Injuries

Osteoporosis

Fractures, Bone

Sarah Farmer, MD

Hanne Vestergaard, MD

This is a clinical study to evaluate the effect of CMPN (Chronic myeloproliferative neoplasm) to the bone.

The hypothesis is that patients with CMPN have a higher fracture-rate compared to the background population. We expect to find a lower BMD using conventional DXA scan (dual energy x-ray absorptiometry), and a change in other parameters using HR-pQCT (high-resolution peripheral quantitative computerized tomography).Biochemical bone markers is measured to support the hypothesis.

This is a clinical study to evaluate the effect of CMPN to the bone.

Three individual cohorts are defined; a cohort consisting of 50 patients with Polycythemia Vera (PV), a cohort consisting of 50 patients with Essential Thrombocythemia (ET), and a cohort consisting of 25 patients with Primary Myelofibrosis (PMF).

Patients are recruited from the Department of Hematology, Odense University Hospital.

Interventions consist of:

* Conventional DXA scan to measure Bone Mineral Density (BMD).
* Experimental HR-pQCT to assess geometry, strength and microstructure of the bone in 3 dimension.
* Blood-samples are collected and frozen for later analyses of Biochemical Bone Markers: 1-CTP, Ctx, ALP (alkaline phosphatase)and P1NP.

The outcome is compared to healthy control individuals.

Blood samples to compare groups and to look for endocrine abnormalities

Myeloproliferative Neoplasms and Bone Structure

Patients will undergo one DXA scan independent of time of CMPN diagnosis

Patients will undergo one HR.pQCT indepedent of the time of the diagnosis of CMPN

University of Southern Denmark

Essential Thrombocythemia

In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily.

Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

NS-018

Srdan Verstovsek, M.D., Ph.D.

The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Phase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QD

Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.

Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.

Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography \[CT\] scan for patients not able to tolerate MRI).

Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.

Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed "complete remission (CR) + partial response (PR) + clinical improvement (CI)" during the treatment period.

Change from baseline in spleen size was assessed by palpation.

MF SAF is a 20-item instrument comprised of 4 subscales: 1) the Brief Fatigue Inventory \[= average of 9 fatigue scores\], 2) Splenomegaly associated symptoms \[= average of 4 splenomegaly and associated scores\], 3) Catabolic/proliferative Symptoms \[= average of 3 catabolic/proliferative associated scores\] and 4) Overall Quality of Life. The items were on a scale from 1 to 10 where 1= most favorable, and 10= least favorable.

Symptoms are evaluated by the MPN-SAF Total Symptom Score (TSS). The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires \>50% reduction in the MPN-SAF TSS.

The JAK2 V617F allele burden mean changes from baseline (%) are presented as pharmacodynamics parameters.

The Phospho-STAT3 mean changes from baseline (%) are presented as pharmacodynamics parameters.

For phospho-STAT3 values (Phase 2 only), study samples were incubated (± IL-6) and labeled with CD markers. Surface markers included CD3+ (CD4+ \[helper T cells\] and CD8+ \[cytotoxic T cells\]) and CD14+ (monocytes) to which intracellular phospho STAT3 was targeted. The levels of phospho-STAT3 in CD14+, CD3+CD4+ and CD3+CD8+ cell subtypes were quantified. Phosphorylated-STAT3 levels were evaluated in the cell types before and after IL-6 incubation (stimulation) and reported both as mean fluorescence intensity (MFI) and the percentage of positive cells. For each sample time point, the MFI was normalized to a fold change.

The fold change was calculated by MFI after IL-6 treatment/MFI before IL-6 treatment. The percent positive cells were normalized by subtracting the percent positive cells before IL-6 treatment from the percent positive cells after IL-6 treatment.

To determine the Cmax as pharmacokinetic parameters of NS-018.

To determine the Tmax as pharmacokinetic parameters of NS-018.

To determine the AUC0-24 as pharmacokinetic parameters of NS-018.

To determine the t½ as pharmacokinetic parameters of NS-018.

To determine the AR as pharmacokinetic parameters of NS-018. AR was calculated as AR = (AUC0-24) Cycle 2 Day 1/ (AUC0-24) Cycle 1 Day 1.

NS Pharma, Inc.

Safety population: NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Totals are based on number of patients and not on dose-level cohort. Patients can appear in more than one dose-level cohort.

Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 75 mg QD

Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 125 mg QD

Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 200 mg QD

Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 300 mg QD

Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 400 mg QD

Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 100 mg BID

Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 200 mg BID

Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 250 mg BID

Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 300 mg BID

Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1: 400 mg BID

Part 2: 300 mg QD

Total

Part 1

Part 2

For Age continuous, Part 1 and Part 2 data are presented in different rows (48+29=77).

Age, Continuous

Sex: Female, Male

White/Caucasian

Black/African Heritage

Asian/Oriental

Other

Race/Ethnicity, Customized

Medical Affairs

Not TEAE

Any AE

Any Treatment Emergent AE

Drug Related TEAE

Any Serious TEAE

TEAE Leading to Discontinuation of study drug

Hospitalization or Prolongation of Existing Hospitalization

Death

The safety population included all patients who received at least 1 dose of study drug.

NS-018-101 study was dose-finding study, Principal investigator (PI) could increase or decrease dose-level per protocol. Totals are based on number of patients and not on dose-level cohort. Patients can appear in more than one dose-level cohort.

Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event

The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)

Part 2: Change From Baseline in Spleen Size

Part 2: Change From Baseline in Bone Marrow Assessment

The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort.

For 300 mg QD, data from 7 patients were available. 4 patients were enrolled originally and 2 patients were dose-reduced from 400 mg QD and 1 patient was dose-reduced from 250 mg BID.

Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort.

At 200 mg BID cohort, 3 patients were enrolled originally, 2 patients were dose-escalated from 100 mg BID cohort and 8 patients were dose-reduced from 300 mg BID or 400 mg BID cohort.

Part 1: Change From Baseline in Spleen Size

Part 1: Change From Baseline in Bone Marrow Assessment

Brief Fatigue Inventory Score

Splenomegaly-associated Symptom Score

Catabolic/Proliferative Symptoms Score

Overall Quality of Life Score

Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF)

Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10)

The PD population included all patients who received at least one dose of study drug and had a baseline and at least one post-baseline PD assessment (for at least one PD parameter). Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels

Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells

Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells

Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells

Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells

Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells

Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells

Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells

Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells

Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells

The PD population included all patients who received at least one dose of study drug and had a baseline and at least one post-baseline PD assessment (for at least one PD parameter). Here, number analyzed reflects number of patients evaluated on that specific cycle day.

Data from 17 out of 24 participants were available and contributed to the analysis. Samples from 7 patients were analyzed, but data were not available due to quantities not sufficient.

Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3)

Cycle 1 Day 1

Cycle 1 Day 8 (Part 1 only)

Cycle 1 Day 15 (Part 2 only)

Cycle 2 Day 1

The PK population include all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, Here, number analyzed reflects number of patients evaluated on that specific cycle day.

Part 2: 1 patient was completely excluded from PK Population due to critical samples missing, 1 patient was excluded from the analysis due to sample missing at timepoint, So the overall number of participants was 27.

Part1 and Part 2: Observed Maximum Concentration (Cmax)

Patients self-administered orally 250 mg of NS-018 twice daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.

Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax)

Cycle 2 Day 1 (Part 1 only)

The PK Population includes all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, regardless of whether derived from parent drug or metabolites.

Part 2: One patient was completely excluded from the PK Population due to critical samples missing; Two patients were excluded from the analysis due to sample missing at time point. so the overall number of participants analyzed was 26.

Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24)

Part 1 and Part 2: Terminal Elimination Half-life (t½)

The PK Population includes all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile (i.e. at least Cmax and AUC evaluable), regardless of whether derived from parent drug or metabolites.

Part1 and Part 2: Accumulation Ratio (AR)

Whole Study

Dose Finding Period - Escalation

Dose Finding Period - Reduction

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antisickling Agents

Interferons

Hydroxyurea

Interferon-alpha

Interferon-alfa-1b

Patients with a diagnosis of polycythaemia vera.

Patients with a diagnosis of essential thrombocythaemia.

No cytoreductive treatment vs cytoreductive drugs (hydroxycarbamide, alpha-interferon, ruxolitinib).

No cytoreductive vs cytoreductive drugs

Yan Beauverd

Myeloproliferative neoplasms (MPN) such as Polycythemia Vera (PV) and, Essential Thrombocythaemia (ET) are rare clonal myeloid neoplasms associated with an increased risk of both venous and arterial thrombosis. Thrombotic complications are the main determinant of morbidity and in a less extend mortality.

Routine haemostasis analysis (TP, aPTT) are usually normal and are useless to demonstrate a hypercoagulable state. However, previous evidence suggests that global coagulation tests such as thrombin generation or thromboelastometry are able to detect signs of procoagulant imbalance in MPN. Similarly, current data seems to demonstrate that fibrin clot properties (clot permeability, turbidimetry, clot lysis time) properties is altered suggesting an hypercoagulable state.

Goals of PV and ET treatments are to control blood count to reduce the risk of thrombotic events. Moreover, new drugs such as Janus Kinase Inhibitors (JAKi) were recently licensed for PV and are under investigations on clinical trial for ET. It is currently unknown if treatments that were used for ET and PV, and especially JAKi are able to modify the hypercoagulable state that is observed in those diseases, and if there is difference between drugs.

To evaluate impact of MPN treatment on prothrombotic haemostatic profile, we propose to evaluate global coagulation and fibrin clot properties in MPN, depending on the treatment.

Treatment of Polycythaemia Vera and Essential Thrombocythaemia: Influence on the Clot Structure

Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report lag-time (seconds).

Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report maximal absorbance.

Fibrinolysis will be assessed by turbidity assay on plasma. Fibrinolysis will be monitored by adding tissue plasminogen activator (tPA). Results will report clot lysis time (minutes)

Clot permeation will be reported as the calculated permeation coefficient (Ks).

The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Endogenous thrombin potential will be reported in nM\*minutes.

The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Peak will be reported in nM.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Extension Study of Bomedemstat (IMG-7289/MK-3543) in Participants With Myeloproliferative Neoplasms (IMG-7289-CTP-202/MK-3543-005)	NCT05223920	Thrombocythemia... Primary Myelofi...	Bomedemstat	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
A Safety Study of XL019 in Adults With Myelofibrosis	NCT00522574	Myeloproliferat... Myelofibrosis Polycythemia Ve... Thrombocythemia...	XL019	18 Years -	Exelixis
Myeloproliferative Neoplasms and Bone Structure	NCT01816022	Polycythemia Ve... Thrombocythemia... Primary Myelofi...		18 Years -	University of Southern Denmark
Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF	NCT01423851	Primary Myelofi... Post-Polycythem... Post-Essential ...	NS-018	18 Years -	NS Pharma, Inc.
Treatment of Polycythaemia Vera and Essential Thrombocythaemia: Influence on the Clot Structure	NCT02912884	Polycythemia Ve... Thrombocythemia...	No cytoreductiv...	18 Years -	University Hospital, Geneva
A Study to Evaluate Safety and Efficacy of Bomedemstat (MK-3543-017)	NCT06351631	Thrombocythemia... Primary Myelofi... Myelofibrosis Post-polycythem... Post-essential ... Polycythemia Ve...	Bomedemstat	18 Years -	Merck Sharp & Dohme LLC
Myeloproliferative Neoplasms and Bone Structure	NCT01816022	Polycythemia Ve... Thrombocythemia... Primary Myelofi...		18 Years -	University of Southern Denmark
A Study in Myeloproliferative Disorders	NCT01134120	Myeloproliferat... Thrombocythemia... Polycythemia Ve... Primary Myelofi...	LY2784544	18 Years -	Eli Lilly and Company
Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF	NCT01423851	Primary Myelofi... Post-Polycythem... Post-Essential ...	NS-018	18 Years -	NS Pharma, Inc.

Spots Global Cancer Trial Database for thrombocythemia, essential