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A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis

NCT03222609

Description:

This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with myelofibrosis.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis
  • Official Title: A Phase 2 Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Subjects With Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: M16-109
  • SECONDARY ID: 2017-001398-17
  • NCT ID: NCT03222609

Conditions

  • Myelofibrosis (MF)

Interventions

DrugSynonymsArms
RuxolitinibJakafiNavitoclax + ruxolitinib
NavitoclaxABT-263Navitoclax + ruxolitinib

Purpose

This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with myelofibrosis.

Trial Arms

NameTypeDescriptionInterventions
Navitoclax + ruxolitinibExperimentalParticipants will be administered navitoclax once daily (QD) at various doses and a dose greater than or equal to 10 mg of ruxolitinib twice daily (BID).
  • Ruxolitinib
  • Navitoclax
NavitoclaxExperimentalParticipants will be administered various doses of navitoclax once daily (QD)
  • Navitoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Participants with documented diagnosis of intermediate or high-risk primary
             Myelofibrosis, post polycythemia Vera Myelofibrosis or post-essential thrombocythemia
             myelofibrosis

          -  Participant must be ineligible or unwilling to undergo stem cell transplantation at
             time of study entry

          -  ECOG of 0,1, or 2.

          -  Participant must have either received prior treatment with ruxolitinib OR another
             JAK-2 inhibitor therapy OR must not have received any prior treatment with JAK-2
             inhibitor.

          -  Participant has splenomegaly as defined in the protocol.

          -  Participant must meet the laboratory parameters (adequate bone marrow, renal and
             hepatic function) as defined in the protocol.

        Exclusion Criteria:

          -  Splenic irradiation within 6 months prior to screening, or prior splenectomy.

          -  Leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).

          -  Participant is currently on medications that interfere with coagulation (including
             warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg)
             and Low-molecular-weight heparin.

          -  Prior therapy with a BH3 mimetic compound.

          -  Participant has received strong or moderate CYP3A inhibitors within 14 days prior to
             the administration of the first dose of navitoclax.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline
Time Frame:From Baseline (Week 0) through Week 24
Safety Issue:
Description:Reduction in spleen volume is measured by magnetic resonance imaging (MRI).

Secondary Outcome Measures

Measure:Percent Change in Total System Score (TSS)
Time Frame:From Baseline (Week 0) through Week 24
Safety Issue:
Description:TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0.
Measure:Overall Response Rate (ORR)
Time Frame:Up to approximately 96 weeks
Safety Issue:
Description:To determine the overall response rate (ORR defined as the sum of rates of complete remission [CR] + partial remission [PR]) according to the IWG criteria.
Measure:Anemia Response Rate
Time Frame:Every 12 weeks up to approximately 96 weeks
Safety Issue:
Description:The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
Measure:Change in Degree of Bone Marrow Fibrosis
Time Frame:Evaluated at Week 12, 24, 48 and 96
Safety Issue:
Description:Change in degree of bone marrow fibrosis from baseline as assessed by bone marrow biopsy.
Measure:Maximum Observed Plasma Concentration (Cmax)
Time Frame:Week 0 Day 1
Safety Issue:
Description:Maximum Observed Plasma Concentration (Cmax)
Measure:Time to Cmax (peak time, Tmax)
Time Frame:Week 0 Day 1
Safety Issue:
Description:Tmax defined as time to maximum observed plasma concentration.
Measure:Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt)
Time Frame:Week 0 Day 1
Safety Issue:
Description:Area under the plasma concentration-time curve from time zero to the last measureable concentration

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Post-polycythemia vera MF (PPV-MF)
  • Post-essential thrombocythemia (PET-MF)
  • ruxolitinib
  • navitoclax
  • splenic volume
  • Primary Myelofibrosis
  • Jakafi
  • enlarged spleen
  • splenomegaly
  • ABT 263
  • bone marrow fibrosis

Last Updated

December 10, 2019