Myelofibrosis: Phase 3 Study of Navitoclax Plus Ruxolitinib Versus Ruxolitinib
- Conditions
- MyelofibrosisMedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000097-15-BE
- Lead Sponsor
- AbbVie Deutschland GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 230
• Subject = 18 years of age.
• Subject with a documented diagnosis of primary myelofibrosis (MF) or secondary MF (post polycythemia vera [PPV] -MF or post essential thrombocythemia [PET] – MF) as defined by the World Health Organization classification.
• Subject must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) on at least 4 out of 7 days prior to randomisation.
- Subject classified as intermediate-2 or high-risk MF as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
• Subject has splenomegaly defined as spleen palpation measurement = 5 cm below costal margin or spleen volume = 450 cm^3 as assessed centrally by MRI or CT scan.
• Subject has at least 2 symptoms measurable (score = 3) or a total score of = 12, as measured by the MFSAF v4.0.
• Subject with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 138
• Subject must not have received prior treatment with a JAK-2 inhibitor.
• Subject must not have received prior treatment with a BH3-mimetic compound or bromodomain and extra-terminal motif (BET) inhibitor.
• Subject must not be eligible 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.
• Subject must not receive 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Week 24;Main Objective: To evaluate the effect of navitoclax in combination with ruxolitinib on splenomegaly response when compared to ruxolitinib in subjects with myelofibrosis.;Primary end point(s): At least 35% reduction in spleen volume from baseline as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, per International Working Group (IWG) criteria.;Secondary Objective: • To evaluate the effect of navitoclax in combination with ruxolitinib on the onset, magnitude, and duration of disease response, including Total Symptom Score (TSS), effects on spleen, bone marrow fibrosis, and anemia.<br>• To evaluate the effect of navitoclax in combination with ruxolitinib on measures of health-related quality of life (HRQoL), including fatigue, and physical functioning.<br>• To evaluate the effect of navitoclax in combination with ruxolitinib on overall survival (OS) and leukemia-free survival.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Change in total symptom score (TSS) at Week 24 from baseline as measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0<br>• Duration of SVR35<br>• Change in fatigue at Week 24 from baseline as measured by the PROMIS Fatigue SF 7a<br>• Change in physical functioning at Week 24 from baseline, as measured by the physical functioning domain of the EORTC QLQ-C30<br>• Anemia response per IWG criteria<br>• At least 35% reduction in spleen volume from baseline (SVR35) as measured by MRI or CT scan, per IWG criteria<br>• Reduction in grade of bone marrow fibrosis from baseline as measured by the European consensus grading system<br>• Overall survival<br>• Leukemia-free survival;Timepoint(s) of evaluation of this end point: Week 24, Time to event, Every 12 weeks