Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Myeloproliferative Disorders

Thrombocytosis

Thrombocythemia, Essential

Blood Platelet Disorders

Hematologic Diseases

Bone Marrow Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

Gastrointestinal Agents

All Drugs and Chemicals

Antineoplastic Agents

Antisickling Agents

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Calcium Carbonate

Hydroxyurea

Anagrelide

Ropeginterferon alfa-2b (P1101) dosage: from 250 mcg to 500 mcg

Ropeginterferon alfa-2b

Anagrelide dosage: 0.5 mg per capsule, according to label and physician's judgement

Toshiaki Sato, MD/PhD

Craig Zimmerman, PhD

This is a Phase 3 open-label, multicenter, randomized, active-controlled study designed to compare the efficacy and safety and tolerability of P1101 compared with ANA after 12 months of treatment as second-line therapy for subjects with ET who have had a suboptimal or failed response to HU.

PharmaEssentia Corporation is developing a pegylated (PEG) IFN-α product, P1101, for the treatment of ET.

Available clinical data and experience with P1101 in PV shows that the compound, with proper dose modifications, is effective in controlling disease in a significant proportion of subjects with ET. Further, its increased serum half-life presents distinct advantages for ET treatment over that of standard IFN-α and other available PEG IFN-α therapy. This pivotal Phase 3 study will establish the efficacy and safety of P1101 in ET subjects.

In core study phase, the enrolled subjects will be randomized into two arms, the test arm is P1101, the control arm is ANA. The overall duration for each eligible patient is 14 months, including screening (1 month), treatment (12 months) and follow-up (1 month) period. Efficacy evaluations, safety assessments, and PK and immunogenicity evaluations of P1101 will be performed.

Evaluation of efficacy will include clinical laboratory assessments, allelic burden measurements of CALR, JAK-2, and MPL, spleen size measurements, bone marrow sampling, EQ-5D-3L, and MPN-SAF TSS completion.

Evaluation of safety will include assessing vital signs, clinical safety laboratory tests, physical examinations, ECG evaluation, heart ECHO, lung X-ray, ECOG performance status, ocular examination, and AEs.

Subjects who completed the end of treatment (EoT) and safety follow-up (EoS) visits of the SURPASS ET study and may benefit from P1101 therapy have the opportunity to receive P1101 treatment.

Experimental Drug (Biological): Ropeginterferon alfa-2b (P1101), Q2W, SC injection Control Drug: Anagrelide, capsules, daily, p.o.

Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance

A Phase 3, Open-Label, Multicenter, Randomized, Active-controlled Study to Assess PK and Compare the Efficacy, Safety, and Tolerability of P1101 vs Anagrelide as 2nd Line Therapy for Essential Thrombocythemia (SURPASS ET): The Core Study and Its Extension Study.

platelets ≤400 x 10\^9/L AND white blood cells (WBC) \<9.5 x 10\^9/L

based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

absence of hemorrhagic or thrombotic events

PharmaEssentia

Neoplasms

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Bone Marrow Neoplasms

Hematologic Neoplasms

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Subjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Given 3 times a week, every other week in 28-day cycles.

panobinostat

ruxolitinib

Novartis Pharmaceuticals

This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).

In 2011 the treatment goals for MF focused on symptom-orientated palliation and quality of life. Both ruxolitinib and panobinostat, as single agents, had shown significant improvement in both of those treatment goals and ruxolitinib had also shown greater reductions in splenomegaly compared to the standard of care at that time. To further the benefit seen with ruxolitinib in MF patients, panobinostat was added to the treatment regimen to act synergistically in the blockade of the dysregulated pathway driving this disease.

The study was conducted in 2 phases - an escalation phase and an expansion phase.

Escalation phase: the study utilised the Bayesian Logistic Regression Model (BLRM), incorporating escalation with overdose control (EWOC), which is a well established method for dose escalation in oncology trials. Following this process, successive cohorts of 3 newly enrolled patients received increasing doses of ruxolitinib and panobinostat until the maximum tolerated dose (MTD) or recommended phase II dose (RPIID) was determined. Once the MTD and/or RPIID were suspected in a minimum of 3 patients, additional patients were enrolled to the same cohort level to reach a minimum of 9 evaluable patients. The process also included safety, PK/PD assessments and estimates of efficacy based on measures of splenic reduction at each dose level.

Expansion: following the determination of the MTD and/or RPIID, a dose expansion phase was conducted at that dose to further define the safety and tolerability of the combination. At least 13, and no more than 23, additional patients were to be enrolled into the expansion phase.

Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis

A Phase 1b, Open-label, Multi-center, Single Arm, Dose Finding Study to Assess Safety and Pharmacokinetics of the Oral Combination of Panobinostat and Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera-myelofibrosis (PPV-MF) or Post-essential Thrombocythemia-myelofibrosis (PET-MF)

Area under the plasma concentration versus time curve

Tmax: The time of maximum observed concentration sampled during a dosing interval.

Symptoms and General Pathology

Disease Progression

Urological Agents

Mirabegron

Adrenergic Agents

Adrenergic beta-3 Receptor Agonists

Adrenergic beta-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Mirabegron treatment of at least 24 weeks with an initial dose of 25 mg daily during the first week followed by 50 mg Mirabegron daily during the remaining treatment period.

25 mg daily during the first week followed by 50 mg Mirabegron daily during the remaining treatment period.

Jakob R. Passweg, Prof

Radek Skoda, Prof

The aim of this phase II study is to test a novel concept in the treatment of patients with myeloproliferative neoplasms (MPN), a disease of the bone marrow. With no current cure available, MPN are a group of chronic leukemias (blood cancers) in which patients produce too many blood cells. These increased blood cell numbers cause problems to the patient such as bleedings or thrombosis and some patients may progress to acute leukemia, a life threatening condition. Most MPN patients have a gene mutation called JAK2-V617F. The disease is maintained by mutant MPN stem cells that reside in the bone marrow in specialized locations called "niches". These niches need connections to the nervous system. New findings show that these connections are destroyed by the presence of the mutated MPN stem cells. Research teams found that some drugs (beta3-sympathicomimetics) can restore these damaged niches and at the same time reduce the MPN disease manifestation in a mouse model of MPN. Such sympathicomimetic drugs are already being used to treat patients with asthma or hyperactive bladder. These drugs have shown to have only few side effects. The study tests the effects of the beta-3-sympathicomimetic drug Mirabegron (Betmiga®) on MPN disease in 39 patients that carry a JAK2-V617F mutation. The hypothesis is that Mirabegron will have a beneficial effect on bone marrow niche cells and will thereby improve the disease manifestation in MPN patients. This study should provide a rapid answer whether targeting the nervous system of the niche cells could be useful for patients with MPN and warrants to be tested in larger and more long-term studies.

DISEASE BACKGROUND

Myeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by aberrant proliferation of the erythroid, megakaryocytic and myeloid lineages. They are associated with decreased survival, thromboembolic complications, hemorrhage and an inherent tendency towards leukemic transformation. About 4-6 of 100'000 residents per year are diagnosed with MPN Currently, MPN are subdivided into three disease entities: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Three genes are frequently mutated in MPN and are implicated to be the phenotypic driver mutations: more than 95% of PV patients carry a somatic JAK2-V617F mutation, while about half of the remaining PV patients (2-3%) display mutations in JAK2 exon 12. Thus, almost all patients with PV have somatic mutations in the JAK2 gene. The mutational profiles of ET and PMF are more diverse: JAK2-V617F is found in 50-60% of the patients, whereas the recently described mutations in calreticulin (CALR) occur in 20-25% of the patients. Between 5-8% of the remaining ET and PMF patients carry mutations in the thrombopoietin receptor (MPL) and in 10-15% of the patient the mutation remains to be determined. Quantitative tests are now available to follow the mutant allele burden of each of the JAK2, CALR and MPL mutant alleles.

THERAPY BACKGROUND

No curative treatment exists for MPN, possibly with the exception of allogeneic hematopoietic stem cell transplantation (HSCT), which is applicable only in a minority of patients. Currently, treatments for MPN are not very effective, or extremely costly. Hydroxyurea has been the standard of care for many decades. A reduction in thrombotic complications can be demonstrated in "high risk" MPN patients (age \>60, presence of a previous thrombotic event), but hydroxyurea has no effect on the course of disease (no remission or substantial reduction of the mutant allele burden). Interferon alpha (IFNα) is a promising treatment for early stage PV and is currently being tested in phase III studies. However, IFNα is not always well tolerated and in phase II studies only a proportion of patients showed a substantial response. Ruxolitinib, recently approved for PMF with splenomegaly, is effective in reducing spleen size and improving quality of life, but has little effect on the JAK2-V617F mutant allele burden and has so far not been reported to induce remissions. Allogeneic HSCT is reserved for patients with PMF with a poor prognostic score. These including the recently developed JAK2 inhibitors reduce the symptoms of the disease, but, with the exception of pegylated interferon alpha (peg-IFNα), have little effect on the size of the neoplastic clone and are unable to induce molecular remissions. Thus, the percentage of mutant allele burden in hematopoietic cells does not change much even with successful treatment when considering symptom reduction. It is generally expected that reduction in the size of the malignant clone, as a surrogate marker of treatment success, will have the potential to reduce morbidity and result in prolonged survival of patients.

NOVEL TREATMENT

The beta-3-sympathicomimetic drug Mirabegron is currently available as Betmiga® and indicated to treat hyperactive bladder. It is available as a slow release tablet in a 25 mg and 50 mg formulation. Sympathicomimetic drugs are known to relax the smooth muscle in several areas of the human body and are therefore used for inhalation in patients with asthma or as described for this drug to relax the smooth muscle of the bladder to treat urge incontinence. β3-Adrenoceptors mediate a negative inotropic effect in human ventricular cardiomyocytes, which is opposite to that of β1- and β2-adrenergic receptors. Unlike beta1/2-mimetics, that have significant cardiovascular side effects (including hypertrophy), beta3-mimetics have been reported to protect from hypertrophy and are only associated with some risk of tachycardia and palpitations in some patients.

Sympathicomimetic agonists in patients with JAK2-mutated MPN

RATIONALE FOR PERFORMING THE TRIAL

MPN is initiated and maintained from a mutated hematopoietic stem cell (HSC). The interplay between the MPN HSCs and the stem cell niche is increasingly recognized as crucial for the biology of the disease. Dr. Simon Méndez-Ferrer et al, previously demonstrated that nestin-positive mesenchymal stem cells (nestin+ MSCs) within the bone marrow niche are innervated by sympathetic nerve fibers and are important in regulating normal HSCs. New findings by Dr. Méndez-Ferrer's laboratory show that these nestin+ MSCs are strongly reduced in bone marrow from patients with MPN.

Furthermore, in a mouse model of MPN expressing the human JAK2-V617F mutation, this effect was found to be caused by early glial and sympathetic nerve damage and apoptosis of nestin+ MSCs triggered by the mutant HSCs. In vivo depletion of nestin+ cells accelerated MPN progression. Conversely, MPN phenotype could be reversed by compensating for the sympathetic neuropathy by the treatment with a beta-3-sympathicomimetic drug. Mice with JAK2-V617F driven MPN treated with a beta-3-sympathicomimetic agonist not only restored nestin+ MSCs numbers, but also showed correction of thrombocytosis, neutrophilia, and bone marrow fibrosis, and efficiently reduced mutant hematopoietic progenitor numbers in bone marrow and peripheral blood. Thus, treatments with a beta-3 sympathicomimetic agonist corrected the damage inflicted by the MPN clone on the stem cell niche and led to a dramatic improvement of the MPN phenotype. Therefore, beta-3 sympathicomimetic agonists represent a promising novel therapeutic approach to MPN by targeting the stem cell niche rather than the MPN clone itself.

Considering the widely used and established safety track record of beta-3-sympathicomimetic drugs, a phase II study has been selected to test the concept of a beneficial effect of beta sympathicomimetic activity on bone marrow niche cells and through this effect on the disease manifestation in MPN patients.

Sympathicomimetic Agonist in Patients With Myeloproliferative Neoplasms With JAK2-mutation

Effects of Sympathicomimetic Agonists on the Disease Course and Mutant Allele Burden in Patients With JAK2-mutated Myeloproliferative Neoplasms. A Multicenter Phase II Trial.

Primary endpoint of the trial is reduction in the burden of mutated alleles of ≥50% at 24 weeks (Red-50@24). Patients are defined as success for this endpoint, if they show a reduction of the JAK2-V617F allelic burden of 50% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. All other evaluable patients will be considered as failures for this endpoint.

Reduction in the burden of mutated alleles of ≥50% at 12 weeks (Red-50@12) defined in the same way as the primary endpoint, but evaluated at 12 weeks ± 4 weeks after registration.

Reduction in the burden of mutated alleles of ≥25% at 24 weeks (Red-25@24): Patients are defined as success for the Red-25@24 endpoint, if they show a reduction of the Jak2-V617F allelic burden of 25% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. All other evaluable patients will be considered as failures for this endpoint.

Reduction in the burden of mutated alleles of ≥25% at 12 weeks (Red-25@12) defined in the same way as the Red-25@24 endpoint, but evaluated at 12 weeks ± 4 weeks after registration.

Swiss Group for Clinical Cancer Research

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoproliferative Disorders

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphoma, Non-Hodgkin

Neoplasms, Plasma Cell

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

200 mg twice daily (with possible dose reduction to 100 mg twice daily)

Patients will receive continuous treatment until progressive disease, toxicity, or until any other condition for treatment discontinuation has been met.

Pacritinib

Ryan Wilcox, MD, PhD

This trial will determine the safety and tolerability of Pacritinib in patients with relapsed/refractory lymphoproliferative disorders.

Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

Phase Ib, Open Label, Single Center Study of Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

Dose limiting toxicity (DLT) rate during the 1st cycle (28 days) of pacritinib.

Overall response rate (ORR), defined as best disease response recorded from first day of treatment until disease progression or initiation of new antineoplastic therapy.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

DOR, defined as time from documented remission to the time of death, relapse, or initiation of alternative antineoplastic.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

Time to next treatment, defined as time from first dose of pacritinib to initiation of alternative antineoplastic therapy

University of Michigan Rogel Cancer Center

Ropeginterferon alfa-2b subcutaneously (SC) every two weeks (± 3 days), target optimal dose of 500 µg. Phlebotomy should be conducted when Hct ≥ 45%.

Phlebotomy only and should be conducted when Hct ≥ 45%.

Ropeginterferon alfa-2b subcutaneously (SC) every two weeks (± 3 days), 250 µg at Day 1, 350 µg at Week 2, and target optimal dose of 500 µg at Week 4.

Control group patients will receive phlebotomy only

Phlebotomy

Ting-Fang Wang

Evan Huang

This is a randomized, open-label, multicenter, two-arm study to assess the efficacy and safety of ropeginterferon alfa-2b for patients with low-risk PV. Approximately 110 patients with low-risk PV will be enrolled. The whole study period is 108 weeks, including a main treatment phase (56 weeks), an extension treatment phase (48 weeks), and a safety follow-up phase (four weeks).

Efficacy and Safety of Ropeginterferon Alfa 2b (P1101) for Patients With Low-Risk Polycythemia Vera

Efficacy and Safety of Ropeginterferon Alfa 2b (P1101) for Patients With Low-Risk Polycythemia Vera - A Randomized Open Label Multicenter Study

Neoplasm Metastasis

AZD1480 until Maximum Tolerated Dose (MTD) is reached

AZD1480

Gregory Curt, MD

This study is being conducted to assess the safety, tolerability and PK of AZD1480 in patients with advanced solid malignancies.

Study to Assess Safety, Tolerability and PK of AZD1480 in Patients With Solid Tumours

A Phase I, Open-Label, Multi-Center, Dose-Escalation Study to Assess the Safety and Tolerability, and Pharmacokinetics of AZD1480 Administered as Daily Oral Monotherapy in Patients With Advanced Solid Malignancies in the Escalation Phase and EGFR or ROS Mutant NSCLC or Non-Smokers With Lung Metastasis in the Expansion Phase.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance	NCT04285086	Essential Throm...	Ropeginterferon... Anagrelide	18 Years -	PharmaEssentia
Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis	NCT01433445	Idiopathic Myel... Post Essential ... Post Polycythem...	panobinostat ruxolitinib	18 Years -	Novartis
Sympathicomimetic Agonist in Patients With Myeloproliferative Neoplasms With JAK2-mutation	NCT02311569	Myeloproliferat... Primary Myelofi... Essential Throm... Polycythemia Ve...	Mirabegron	18 Years -	Swiss Group for Clinical Cancer Research
Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance	NCT04285086	Essential Throm...	Ropeginterferon... Anagrelide	18 Years -	PharmaEssentia
Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders	NCT03601819	Lymphoma, T-Cel... Lymphoma, T-Cel... Chronic Lymphoc... Lymphoprolifera... Waldenstrom Mac... Lymphoplasmacyt... Mantle Cell Lym...	Pacritinib	18 Years -	University of Michigan Rogel Cancer Center
Sympathicomimetic Agonist in Patients With Myeloproliferative Neoplasms With JAK2-mutation	NCT02311569	Myeloproliferat... Primary Myelofi... Essential Throm... Polycythemia Ve...	Mirabegron	18 Years -	Swiss Group for Clinical Cancer Research
Efficacy and Safety of Ropeginterferon Alfa 2b (P1101) for Patients With Low-Risk Polycythemia Vera	NCT06290765	Polycythemia Ve... Myeloproliferat...	Ropeginterferon... Phlebotomy	18 Years - 59 Years	PharmaEssentia
Study to Assess Safety, Tolerability and PK of AZD1480 in Patients With Solid Tumours	NCT01112397	Solid Malignanc...	AZD1480	18 Years -	AstraZeneca

Spots Global Cancer Trial Database for jak2

Every month we try and update this database with for jak2 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.

Spots Global Cancer Trial Database for jak2

Every month we try and update this database with for jak2 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.

Every month we try and update this database with for jak2 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.