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Trial record 1 of 1 for:    NCT02311569
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Sympathicomimetic Agonist in Patients With Myeloproliferative Neoplasms With JAK2-mutation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT02311569
First received: December 4, 2014
Last updated: December 28, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Myeloproliferative Neoplasm Primary Myelofibrosis Essential Thrombocythemia Polycythemia Vera Drug: Mirabegron Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Sympathicomimetic Agonists on the Disease Course and Mutant Allele Burden in Patients With JAK2-mutated Myeloproliferative Neoplasms. A Multicenter Phase II Trial.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Reduction in the burden of mutated alleles of ≥50% at 24 weeks. [ Time Frame: at 24 weeks ]
    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.


Secondary Outcome Measures:
  • Reduction in the burden of mutated alleles of ≥50% [ Time Frame: at 12 weeks ]
    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% [ Time Frame: at 24 weeks ]
    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% [ Time Frame: at 12 weeks ]
    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.


Enrollment: 39
Study Start Date: April 2015
Study Completion Date: December 2016
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm Mirabegron
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.
Drug: Mirabegron
25 mg daily during the first week followed by 50 mg Mirabegron daily during the remaining treatment period.
Other Name: Betmiga®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of JAK2-V617F positive ET, PV or PMF at primary diagnosis or pretreated
  • JAK2-V617F mutant allele burden > 20% in the peripheral blood at study entry
  • Patient must give written informed consent before registration
  • WHO performance status 0-2
  • Age ≥ 18 years
  • Adequate hematological values: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/ L
  • Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN
  • Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault)
  • Women are not breastfeeding. Women with child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during 28 days thereafter. A negative pregnancy test before inclusion (within 7 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 28 days thereafter.
  • Patient compliance and geographic proximity allow proper staging and follow-up.

Exclusion Criteria:

  • Leukemic transformation (>20% blasts in blood, marrow or extramedullary site)
  • Diabetic neuropathy
  • Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, known cardiac rhythm disturbance including atrial fibrillation or QT prolongation
  • Uncontrolled hypertension
  • Treatment of ET, PV or PMF with IFNα or treatment of PMF with JAK inhibitors such as ruxolitinib within 3 months prior to trial entry.
  • Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
  • Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent or interfering with compliance for oral drug intake.
  • Treatment with hematopoietic stem cell transplantation
  • Concurrent treatment with cytoreductive drugs, other experimental drugs or other anti-cancer therapy as well as treatment in a clinical trial within 2 months prior to trial entry.
  • 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. active autoimmune disease, uncontrolled diabetes, uncontrolled infection (HIV, Hepatitis B and C).
  • Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug.
  • Any concomitant drugs contraindicated for use with the trial drug according to the approved product information.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02311569

Locations
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Hopitaux Universitaires de Geneve
Genève 14, Switzerland, 1211
Centre Hospitalier Universitaire Vaudois CHUV
Lausanne, Switzerland, 1011
Kantonsspital Liestal
Liestal, Switzerland, CH-4410
Kantonsspital Luzern
Luzern, Switzerland, CH-6000
Kantonsspital Münsterlingen
Münsterlingen, Switzerland, 8596
Universitätsspital Zürich
Zurich, Switzerland, CH-8091
Stadtspital Triemli
Zürich, Switzerland, 8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Jakob R. Passweg, Prof University Hospital, Basel, Switzerland
Study Chair: Radek Skoda, Prof University Hospital, Basel, Switzerland
  More Information

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT02311569     History of Changes
Other Study ID Numbers: SAKK 33/14
Study First Received: December 4, 2014
Last Updated: December 28, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
JAK2
Mirabegron
Primary myelofibrosis
beta-3-mimetic drugs
Myeloproliferative neoplasm
Essential thrombocythemia
Polycythemia vera
Betmiga
JAK2-V617F

Additional relevant MeSH terms:
Neoplasms
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Myeloproliferative Disorders
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Mirabegron
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents

ClinicalTrials.gov processed this record on August 18, 2017