Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis



Sponsor:   AbbVie


Sommario: 
      Myelofibrosis is a type of bone marrow cancer that usually develops slowly and disrupts
      body's normal production of blood cells. It causes bone marrow scarring, leading to severe
      anemia that can cause weakness and fatigue. It can also cause a low number of blood-clotting
      cells called platelets, which increases risk of bleeding. Myelofibrosis often causes an
      enlarged spleen. The purpose of this study is to see if a combination of navitoclax and
      ruxolitinib is more effective and safe in assessment of change in spleen volume when compared
      to ruxolitinib in participants with myelofibrosis.

      Navitoclax is an investigational drug for the treatment of myelofibrosis. Participants in
      this study are divided into two groups, called treatment arms. Each group receives a
      different treatment. Adult participants with a diagnosis of myelofibrosis will be enrolled.
      Around 230 participants will be enrolled in approximately 190 sites worldwide.

      Participants will receive oral navitoclax tablet with oral ruxolitinib tablet or oral
      ruxolitinib tablet with oral placebo (no active drug) tablet and treatment may continue
      untill the participant cannot tolerate the study drug, or benefit is not achieved, or other
      reasons which qualify for discontinuation of the study drug.

      There may be a higher treatment burden for participants in this trial compared to their
      standard of care. Participants will attend regular visits during the course of the study at a
      hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
      tests, magnetic resonance imaging (MRI) or computed tomography (CT) scan, bone marrow tests,
      checking for side effects, and completing questionnaires.
    




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 3




TRATTAMENTO

  
    
  
  • Navitoclax
  • Ruxolitinib
  • Placebo for Navitoclax
    • 






OBIETTIVO PRIMARIO


  
  • Misura: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24)
  • Tempo: At Week 24
  • Descrizione: Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.




OBIETTIVO SECONDARIO


  
  • Misura: Change in Total Symptom Score (TSS)
  • Tempo: Baseline (Week 0) Up to Week 24
  • Descrizione: Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
  • Misura: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35)
  • Tempo: Baseline (Week 0) Up to Week 96
  • Descrizione: Reduction in spleen volume is measured by MRI or CT, per IWG criteria.
  • Misura: Duration of 35% Spleen Volume Reduction (SVR35)
  • Tempo: Baseline (Week 0) Up to Week 96
  • Descrizione: Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of the first assessment where the spleen volume is less than 35% reduction from baseline and is at least 25% increase from the nadir (the lowest spleen volume).
  • Misura: Change In Fatigue
  • Tempo: Baseline (Week 0) Up to Week 24
  • Descrizione: Change in fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 7a.
  • Misura: Change in Physical Functioning
  • Tempo: Baseline (Week 0) Up to Week 24
  • Descrizione: Change in physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 or death.
  • Misura: Percentage of Participants who achieve Anemia Response
  • Tempo: Baseline (Week 0) Up to Week 96
  • Descrizione: The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
  • Misura: Overall Survival (OS)
  • Tempo: Up To approximately 8 Years
  • Descrizione: OS is defined as the time from the date of randomization to the date of death from any cause.
  • Misura: Leukemia-Free Survival
  • Tempo: Up To approximately 8 Years
  • Descrizione: Leukemia-free survival is defined as the number of days from the date of randomization to the onset date of documented leukemia, disease progression due to leukemia, or death due to leukemia, whichever occurs first.
  • Misura: Percentage of Participants who Achieve Reduction in Grade of Bone Marrow Fibrosis
  • Tempo: Baseline (Week 0) Up to Week 96
  • Descrizione: Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.




CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    
        Inclusion Criteria:

          -  Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health
             Organization (WHO) classification or Secondary MF (post polycythemia vera [PPV] - MF
             or Post Essential Thrombocytopenia [PET] - MF) .

          -  Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out
             of 7 days immediately preceding the date of randomization.

             -- Must have at least 2 symptoms with a score >=3 or a total score of >=12, as
             measured by the MFSAF v4.0.

          -  Classified as intermediate-2, or high-Risk MF as defined by the Dynamic International
             Prognostic Scoring System Plus (DIPSS+).

          -  Has splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below
             costal margin or spleen volume greater than or equal to 450 cubic cm as assessed
             centrally by magnetic resonance imaging (MRI) or computed tomography (CT) scan.

          -  Ineligible for stem cell transplantation at time of study entry due to age,
             comorbidities, or unfit for unrelated or unmatched donor transplant and other criteria
             per National Comprehensive Cancer Network guidelines.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

        Exclusion Criteria:

          -  Prior treatment with a Janus Kinase-2 (JAK-2) inhibitor.

          -  Prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound or
             bromodomain and extra-terminal motif (BET) inhibitor or stem cell transplant.

          -  Receiving medication that interferes with coagulation or platelet function within 3
             days prior to the first dose of study drug or during the study treatment period except
             for low dose aspirin (up to 100 milligram daily) and low molecular weight heparin
             (LMWH).
      
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 18 Years

Età Massima: N/A






LUOGO


  
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 219083
Rome, 00168
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 221907
Bergamo, 24127
IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 220867
Bologna, 40138
ASST Spedali civili di Brescia /ID# 241273
Brescia, 25123
A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 219085
Catania, 95123
Azienda Ospedaliero Universitaria Careggi /ID# 219086
Florence, 50134
ASST Sette Laghi /ID# 219084
Varese, 21100