Heart and Blood Diseases

Blood and Lymph Conditions

All Conditions

Neoplasms

Rare Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Blood Platelet Disorders

Bone Marrow Diseases

Thrombocytosis

Thrombocythemia, Essential

Hematologic Diseases

Hemorrhagic Disorders

Bone Marrow Neoplasms

Hematologic Neoplasms

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

All Drugs and Chemicals

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants with polycythemia vera will receive 100 mg of momelotinib.

Participants with polycythemia vera will receive 200 mg of momelotinib.

Participants with essential thrombocythemia will receive 100 mg of momelotinib.

Participants with essential thrombocythemia will receive 200 mg of momelotinib.

Momelotinib tablet administered orally once daily

Momelotinib

Peter Lee, MD, PhD

This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.

Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

For the PV Cohort, overall response rate (ORR) is defined as the proportion of participants with all of the following at some point during the treatment period:

* Hematocrit \< 45% in the absence of phlebotomy that lasts at least 4 weeks
* White blood cell (WBC) count \< 10 x 10\^9/L that lasts at least 4 weeks
* Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks
* Resolution of palpable splenomegaly that lasts at least 4 weeks

For the ET Cohort, overall response rate is defined as the proportion of participants with all of the following at some point during the treatment period:

* WBC count \< 10 x 10\^9/L that lasts at least 4 weeks
* Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks
* Resolution of palpable splenomegaly that lasts at least 4 weeks

Confirmed overall response rate is defined as the proportion of participants who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks.

Sierra Oncology LLC - a GSK company

Symptoms and General Pathology

Thrombosis

Neoplasm Metastasis

Patients with polycythemia defined as hematocrit level greater than or equal to 49% in men and 48% in women, whatever the suspected etiology. Primitive and secondary polycythemia are eligible in this observational study. Patients should not have start any cytoreductive therapy prior inclusion.

Mael HEIBLIG, MD,PhD

Polycythemia (PG) corresponds to an increase in erythrocyte parameters on a blood test. A distinction is usually made between primary and secondary PG. The most common primary PG is Vaquez's disease, a hematological cancer. In Vaquez disease, an increase in hematocrit has been reported to be associated with a logarithmic increase in blood viscosity.

The main complications of primary PGs (especially in Vaquez disease) are thromboembolic complications. In contrast, thromboembolic complications are rarer in secondary PG. In Vaquez disease, a hematocrit ≤ 45% has been defined as the therapeutic goal for significantly reducing thromboembolic risk. However, this has not been established for secondary PGs. All in all, the definition of the 45% threshold is based solely on clinical studies with no obvious biological argument. What's more, simply lowering blood mass through cytoreduction alone does not appear to be sufficient to significantly reduce thromboembolic risk.

To investigator knowledge, there are no studies prospectively evaluating blood viscosity, its determinants and coagulation in different types of polycythemia. Nor are there any data on the direct effect on blood viscosity of the various treatments usually offered.

Blood Viscosity in Polycythemia Patients

Evaluation of Blood Viscosity and Hyperviscosity-related Complications Relationship in Patients With Patients With Polycythemia

The investigators expect higher blood viscosity values in polyglobulic patients with symptoms of clinical hyperviscosity than in polyglobulic patients without symptoms of clinical hyperviscosity, but no differences in hematocrit between the two polycythemia groups

Hospices Civils de Lyon

Disease Progression

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Antineoplastic Agents

Anti-Infective Agents

Antisickling Agents

Aspirin

Busulfan

Interferons

Hydroxyurea

Anagrelide

Patients with clinically overt PV (and not exhibiting any of the characteristics listed for Cohort B), managed with:

1. Watchful waiting (with or without aspirin)\*, or
2. Phlebotomy (PHL) alone (with or without aspirin)\* - or
3. HU alone (without concomitant PHL, with or without aspirin).

(\*Unless patient has a history of intolerance or clinical resistance/ refractoriness to hydroxyurea \[HU\] (as assessed by the treating physician) - in which case, s/he belongs to Cohort B)

Patients with clinically overt PV, with one or more of the following disease characteristics:

1. Treatment with HU and PHL in combination or
2. Treatment with any agent other than HU or aspirin (e.g., recombinant interferon (IFN) or pegylated IFN preparations, busulfan, anagrelide) or
3. A history of thrombosis (venous or arterial) or
4. A history of intolerance or clinical resistance/ refractoriness to HU (as assessed by the treating physician) or
5. Presence of documented splenomegaly (clinically assessed by palpation) or
6. Presence of one or more of the following uncontrolled symptoms related to PV despite therapy (Symptoms deemed uncontrolled as per physician's judgment)

   1. Tiredness
   2. Difficulty sleeping
   3. Itching
   4. Muscle aches and/or bone pain
   5. Night sweats
   6. Sweats while awake
   7. Other

Robyn M. Scherber, MD, MPH

This is a Phase IV, multicenter, non-interventional, non-randomized, prospective, observational study in an adult population (patients \>18 years old) of men and women who have been diagnosed with clinically overt PV and are being followed in either community or academic medical centers in the United States who will be enrolled over a 12-month period and observed for 36 months from the date the last patient is enrolled.

Blood sample(s), two vials, one with heparin, another with ethylenediaminetetraacetic acid (EDTA) will be collected at enrollment and then annually thereafter until the end of study for serum analysis of proteins and assessment of allele burden and mutations.

Prospective Observational Study Of Patients With Polycythemia Vera In US Clinical Practices (REVEAL)

Prospective, Non-interventional Study of Disease Progression and Treatment of Patients With Polycythemia Vera in United States Academic or Community Clinical Practices

Healthcare resources were defined as a. Medical visits (including Office visits, ER visits, and hospitalizations), b. phlebotomy (PHL) procedures and c. prescriptions (including PV-related prescriptions, PV-related over-the-counter (OTC) medications, and prescription medications for co-morbid conditions).

The MPN-SAF TSS is a validated 10-item instrument that efficiently assesses the prevalence and severity of PV symptoms in both clinical practice and trial settings. Higher scores indicate more severe symptoms and greater inactivity with a possible total score range of 0-100.

WPAI-SHP is a validated 6-item instrument that measures the effect of overall health and specific symptoms on productivity at work and outside of it. All outcomes are presented as a proportion, with 0% representing minimal/no impairment and 100% representing maximal impairment or productivity loss.

The amount of health care received by a paid healthcare worker or by an unpaid caregiver

A patients self-reported assessment of burden including pain at site, difficulty and inconvenience of scheduling and cost factors.

Incyte Corporation

Primary Myelofibrosis

Janus Kinase Inhibitors

Thalidomide

Imetelstat

Motesanib diphosphate

Danazol

Participants will receive imetelstat at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Participants will receive BAT (investigator-selected non-JAK-inhibitor treatment), until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Participants on BAT who meet protocol-defined criteria for progressive disease may crossover to receive imetelstat treatment after sponsor's approval.

Imetelstat will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Non-JAK-inhibitor treatment will be given, which may include but is not limited to hydroxyurea, thalidomide or an analog of thalidomide, interferon, danazol, hypomethylating agents, chemotherapy or radiotherapy.

Best Available Therapy (BAT)

Vivian Rodolf, MD

Jennifer Riggs

Faye Feller

The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory to Janus Kinase (JAK)-Inhibitor treatment.

This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT).

Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.

A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor

Overall survival is defined as the time interval from randomization date to date of death from any cause.

The proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline

Progression-free survival is defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria) or death from any cause, whichever occurs first.

The proportion of participants who achieve a reduction in spleen volume of ≥ 35% from baseline at Week 24.

The proportion of participants achieving CR or PR, CI, spleen response, symptom response, and anemia response per modified 2013 IWG-MRT criteria.

Reduction in the degree of bone marrow fibrosis will be assessed.

Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment

Maximum Observed Plasma Concentration (Cmax).

Time to reach the maximum observed plasma concentration

Area under the drug concentration-plasma time curve (AUC) from time zero to last measurable concentration

Patient-reported outcomes including health-related quality of life, pain, and overall change in participant's health will be assessed using the EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher scores indicated worse outcome.

EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

Geron Corporation

Amino Acids

Peginterferon alfa-2b

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Immunologic Factors

Proline

Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study

AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study

Subjects will continue to receive the dosage which delivers the optimal disease response (hematocrit \[Hct\]\<45%, platelets \[PLTs\]\<400 x 109/L and leukocytes \[WBCs\]\<10 x 109/L), as determined in the PROUD-PV study, preferably at the level of target blood values.

Pegylated-Proline-interferon alpha-2b

Best available therapy as selected by the investigator

Best available therapy (BAT)

Heinz Gisslinger, MD

Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin, fatigue, disturbed blood circulation in the brain as well as fingers and toes and an increased risk of arterial and venous thrombosis (thrombosis is the formation of a blood clot in a vessel); like stroke, cardiac infarction, deep vein thrombosis in the legs. In case of a strong increase of platelets there is an additional risk of bleedings. As the disease progresses the size of spleen and liver increased in most cases and the bone marrow shows signs of fibrosis. In some cases of PV a progression at a later time point to a leukemia (increased formation of white blood cells) can occur.

The aim of this study is to show that the study drug AOP2014 (pegylated proline interferon alpha-2b) has the long term efficacy and safety in controlling the disease. A comparison arm is receiving best available therapy as selected by the investigator. Response to the treatment is measured by several blood parameters as well as size of the spleen.

Interferon-alpha has been shown to be effective in controlling the blood parameters by immunologically influencing the blood building cells. This can lead to a suppression of the disease-causing stem cells and help healthy stem cells to proliferate. Through this mechanism it is possible that Interferon-alpha can avoid long-term damaging effects of the disease.

This is a Phase III, parallel-arm, open-label continuation of the PROUD-PV study performed in adults diagnosed with Polycythemia Vera (PV). Patients who received AOP2014 in the primary study, PROUD-PV will continue on AOP2014, patients who received HU in the PROUD-PV study will receive best available therapy as selected by the investigator. Only patients who completed PROUD-PV including the end of study visit will be enrolled into this continuation study.

AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.

An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study

The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months).

The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct\<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs\<400 x 109/L, WBCs\<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct\<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs\<400 x 109/L, WBCs\<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).

PharmaEssentia Corporation (for the U.S.)

AOP Orphan Pharmaceuticals AG

Pre-filled Syringe, Q2W starting at 250-350-500, SC injection

Pre-filled Syringe, Q2W starting at 100 up to 500 (50mcg increases), SC injection

P1101 (Ropeginterferon alfa-2b-njft)

Ropeginterferon alfa-2b-njft (P1101)

Jewell Jessup, PhD

Poonam Neki

Phil Hutson

Jacob Patterson

Barbie Warner

Leta Ko

Delphine Thomas

Karyn Gordon

Percy Yeung

Noelle Townsend

Mikaela Dougherty

Denise Brigham

Mitchell Davidsz

Suzhen Gong

Nichole Ard

Nicole Fisher

Cory Caldwell

Tathiana Ruiz

Christopher Hillis, PhD

Dana Maassen

Ray Urbanski, MD, PhD

A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients with PV

Polycythemia vera (PV) is the most common type of chronic myeloproliferative neoplasm (MPN), with an annual reported incidence of up to 2.6/100,000. This is a long-term debilitating and life-threatening disease because it is associated with the risk of thrombosis, bleeding, and progression to myelofibrosis (MF) and secondary acute myeloid leukemia (sAML)

Ropeginterferon alfa-2b-njft (P1101), which gained US marketing authorization in November 2021, is the only interferon alfa approved for the treatment of PV.

This study aims to evaluate the efficacy, tolerability, and safety of ropeginterferon alfa-2b-njft (P1101) in US and Canadian PV patients, utilizing an optimized dosing regimen.

A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV

A Phase IIIb, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-njft (P1101) in Adult Patients With Polycythemia Vera (PV)

CHR is defined as hematocrit (HCT) \<45%, white blood cell (WBC) count \<10 × 10\^9/L, platelets (PLT) ≤400 × 10\^9/L in the absence of phlebotomy in the previous 12 weeks.

PharmaEssentia

The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.

CO-Rebreathing technique at diagnosis of polycythemia

Loïc GARCON, professor

Lydia ROY, Doctor

Marjolaine GEORGES, Doctor

The optimized CO-Rebreathing is an efficient method to evaluate the red cell mass and has been used in the vast majority of studies in sport medicine. However, this method has never been evaluated on a large scale in the diagnosis of primitive or secondary polycythemia. The standard procedure to evaluate the red cell mass is based on isotopic measurement using Cr51-labelled red cells, but its lack of availability in many centers highlights the need for a non-invasive and rapid alternative method. The purpose of this study is to evaluate and validate the CO-Rebreathing method in this set of indications.

The definition of a true polycythemia is stricto sensu an increased red cell mass (RCM) above 125% of the expected value depending on the size and the weight of the patient. However, this measurement requires an isotopic labeling of red cells and is not available in most of the hospitals. Therefore, the diagnosis of polycythemia, and particularly Polycythemia Vera (PV) is based on routine red blood cells parameters, i.e. hemoglobin level and hematocrit. If these parameters are efficient in marked polycythemia, discrepancies have been observed in milder cases. Two situations where a RCM evaluation is particularly required can be described:

* In patients with a hematocrit level between 52 and 60% (men) or between 48 and 56% (women) in order to limit invasive investigations to patients with a confirmed polycythemia diagnosis
* In JAK2V617F positive myeloproliferative neoplasms (MPN) with hematocrit and hemoglobin levels under the PV cut-off in order to discriminate between masked PV and essential thrombocythemia CO-Rebreathing is a fast, non invasive alternative method for RCM evaluation. It is based on the high affinity of carbon monoxide (CO) for hemoglobin. The decrease in the HbCO percentage after CO inhalation is dependent on the total hemoglobin mass from which RCM can be obtained. The investigators propose a tri-centric study evaluating CO-Rebreathing as an alternative tool to measure RCM in the diagnosis of polycythemia in the two categories of patients described above.

CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia

CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia: a Multicentric Study. Co-Rebreathing for the Measurement of Total Red Cell Mass in Polycythemia.

The primary outcome is to prove the equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia.

Incidence, grade type according to NCI-CTCAE v4.0

Cumulative incidence of thrombotic and hemorrhagic complications List according to PT1 protocol.

Analysis of the results of VGTCO and VGTi as a function of hemoglobin and hematocrit

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia	NCT01998828	Polycythemia Ve... Essential Throm...	Momelotinib	18 Years -	Sierra Oncology LLC - a GSK company
Blood Viscosity in Polycythemia Patients	NCT06421025	Polycythemia Se... Polycythemia, P...		18 Years -	Hospices Civils de Lyon
Prospective Observational Study Of Patients With Polycythemia Vera In US Clinical Practices (REVEAL)	NCT02252159	MPN (Myeloproli...		18 Years -	Incyte Corporation
A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment	NCT04576156	Myelofibrosis	Imetelstat Best Available ...	18 Years -	Geron Corporation
Blood Viscosity in Polycythemia Patients	NCT06421025	Polycythemia Se... Polycythemia, P...		18 Years -	Hospices Civils de Lyon
AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.	NCT02218047	Polycythemia Ve...	Pegylated-Proli... Best available ...	18 Years -	AOP Orphan Pharmaceuticals AG
A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV	NCT05481151	Polycythemia Ve...	P1101 (Ropegint... Ropeginterferon...	18 Years -	PharmaEssentia
CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia	NCT03008642	Polycythemia	CO-Rebreathing ...	18 Years - 80 Years	Centre Hospitalier Universitaire, Amiens

Spots Global Cancer Trial Database for polycythemia

Every month we try and update this database with for polycythemia cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.