A Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax alone or in Combination with Ruxolitinib in Subjects with Myelofibrosis
- 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
- EUCTR2017-001398-17-IT
- Lead Sponsor
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 164
- Subjects = 18 years of age
- Subjects with documented diagnosis of Intermediate or High-risk
Primary myelofibrosis, post-polycythemia vera myelofibrosis or postessential
thrombocythemia myelofibrosis
- Subjects classified as intermediate-2 or high-risk myelofibrosis, as
defined by the Dynamic International Prognostic Scoring System
(DIPSS)
- Subject must be ineligible or unwilling to undergo stem cell
transplantation at time of study entry
- Subject 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 or BET inhibitor.
- Subject has palpable splenomegaly.
- Subject must meet the laboratory parameters (adequate bone marrow,
renal and hepatic function) as defined in the protocol.
- Cohorts 1b and 3 only: Subject has at least 2 symptoms each with a
score = 3 or a total score of = 12, as measured by the MFSAF v4.0.
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
- Splenic irradiation within 6 months prior to screening, or prior
splenectomy.
- Leukemic transformation (> 10% blasts in peripheral blood or bone
marrow biopsy).
- Subject 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.
- Cohort 1b only: Subject has received strong or moderate CYP3A
inhibitors within 14 days prior to the administration of the first dose of
navitoclax.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the effect of navitoclax alone or in combination with ruxolitinib on spleen volume;Secondary Objective: - To assess the effect of navitoclax alone or in combination with ruxolitinib on total symptom score (TSS) as assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0 diary<br>- To evaluate the effect of navitoclax alone or in combination with ruxolitinib on bone marrow fibrosis<br>- To determine the overall response rate (ORR = sum of rates of complete remission [CR] + partial remission [PR]) associated with navitoclax alone or in combination with ruxolitinib<br>- To determine the rate of anemia response associated with navitoclax alone or in combination with ruxolitinib<br>- To describe the safety profile and PK profile observed with navitoclax alone or in combination with ruxolitinib<br>;Primary end point(s): = 35% spleen volume reduction from baseline (SVR35) at Week 24<br>measured by MRI/CT.;Timepoint(s) of evaluation of this end point: Week 24
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary endpoints are at least 50% reduction in total symptom<br>score from baseline measured by MFSAF 4.0; anemia response; and<br>change in grade of bone marrow fibrosis.;Timepoint(s) of evaluation of this end point: Week 24