avitoclax Monotherapy and in Combination with Ruxolitinib in Myeloproliferative Neoplasm Subjects
- Conditions
- Myeloproliferative Neoplasm
- Registration Number
- JPRN-jRCT2080224824
- Lead Sponsor
- AbbVie GK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 9
Navitoclax Monotherapy (Part 1):
- Documented diagnosis of myelofibrosis (MF), polycythemia vera (PV) or essential thrombocythemia (ET) as defined by the World Health Organization classification.
- MF subjects must have received and failed or are intolerant to ruxolitinib therapy.
- ET or PV subjects must be requiring cytoreduction who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy.
Navitoclax + ruxolitinib Combination Therapy (Part 2):
- Has documented diagnosis of primary MF, post-polycythemia vera MF (PPV-MF), or post-essential thrombocythemia (PET-MF) as defined by the World Health Organization classification.
- Is ineligible or unwilling to undergo stem cell transplantation at time of study entry.
- Has splenomegaly as defined by a spleen palpable >= 5 cm below costal margin or spleen volume >= 450 cm^3 as assessed by magnetic resonance imaging (MRI) or computed topography (CT) scan.
- Must have received ruxolitinib therapy for at least 12 weeks and be currently on a stable dose (as described in the protocol).
- Must have adequate bone marrow, kidney, liver and hematology blood values as detailed in the study protocol.
- Part 1 only: Cytoreduction therapy within 14 days prior to the first dose of navitoclax may be allowed pending additional discussion with study doctor. Ruxolitinib for MF subjects will not be allowed within 7 days prior to the first dose of study drug and during navitoclax administration.
- Shows leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).
- Has a history of an active malignancy other than MPN within the past 2 years prior to study entry (exceptions detailed in the protocol).
- Has a positive test result for HIV at screening.
- Has chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
- Has evidence of other clinically significant uncontrolled condition(s).
- Has previously taken a BH3 mimetic compound.
- Currently on medications that interfere with coagulation or platelet function with the exception of low dose aspirin (up to 100 mg) and low-molecular-weight heparin.
- Has received strong or moderate CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 14 days prior to the administration of the first dose of navitoclax.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method safety<br>pharmacokinetics<br>- Dose Limiting Toxicities (DLT)<br>- Maximum Observed Plasma Concentration (Cmax)<br>- Time to Cmax (peak time, Tmax)<br>- Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt)<br>- Number of Participants with Adverse Events
- Secondary Outcome Measures
Name Time Method efficacy<br>Overall Response Rate (ORR)