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.
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
Interventions
Drug | Synonyms | Arms |
---|
Ruxolitinib | Jakafi | Navitoclax + ruxolitinib |
Navitoclax | ABT-263 | Navitoclax + 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
Name | Type | Description | Interventions |
---|
Navitoclax + ruxolitinib | Experimental | Participants 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). | |
Navitoclax | Experimental | Participants will be administered various doses of navitoclax once daily (QD) | |
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