A randomized, open-label, phase 3 study studying the efficacy and safety of navitoclax in combination with ruxolitinib versus best available therapy in patients relapsed myelofibrosis

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 330

Inclusion Criteria

• Subject = 18 years of age.
•Subject must be able to complete the MFSAF v4.0 on at least 4 out of 7 days immediately prior to to the date of randomisation and must agree to collect MFSAF data daily by ePRO device during the study collection window.
- Subject has at least 2 symptoms with an average score = 3 or an average total score of = 12, as measured by the MFSAF v4.0. Average scores will be calculated from the 7 days immediately prior to the date of randomization, with at least 4 days required to calculate a valid average score.
• Subject with a documented diagnosis of primary MF, post polycythemia vera (PPV)-MF, or post essential thrombocythemia (PET)–MF as defined by the World Health Organization classification, characterized by bone marrow fibrosis grades 2 or 3.
• Subject classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
• Subject must currently be on treatment or have received prior treatment with a single JAK2 inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
- Treatment with ruxolitinib for = 24 weeks that was stopped due to lack of spleen response, or loss of spleen response or symptom control after a previous response, or was continued despite relapsed/refractory status.
- Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy.
• Prior treatment with ruxolitinib of at least 10 mg BID for = 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily dose of ruxolitinib = 30 mg but unable to reduce dose further due to lack of efficacy. Note: Subject must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinib-related = Grade 3 toxicity.
• Subject has splenomegaly defined as palpable spleen measurement = 5 cm below left costal margin or spleen volume = 450 cm^3 as assessed centrally by MRI or CT scan.
• Subject has a baseline platelet count = 100 × 10^9 /L.

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 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

• Subject must not have received prior treatment with a B-cell lymphoma 2 homology 3 (BH3) -mimetic compound, bromodomain extra-terminal (BET) inhibitor, phosphoinositide 3-kinase and telomerase inhibitors (e.g., parsaclisib), prior use of > 1 JAK2 inhibitor or allogeneic stem cell transplant.
• Subject must not be eligible for allogeneic stem cell transplantation at the 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 has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• 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.
• Subject must not receive anticancer therapy including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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