A Phase 2 Single-Arm, Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax in Combination with Ruxolitinib in Subjects with Myelofibrosis
The purpose of this study is to determine the effect of the combination of navitoclax plus ruxolitinib on your cancer Myelofibrosis. The study will evaluate how well the study drug works and the safety of the drug.
The Primary Objective of the study is to:
Evaluate the effect of the addition of navitoclax to ruxolitinib on spleen volume.
The Secondary Objectives of the study are:
To assess the effect of the addition of navitoclax to ruxolitinib on total symptom score (TSS) as assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0 diary.
To evaluate the effect of the addition of navitoclax to ruxolitinib on bone marrow fibrosis.
To determine the overall response rate (ORR = sum of rates of complete remission [CR] + partial remission [PR]) associated with the addition of navitoclax to ruxolitinib.
To determine the rate of anemia response associated with the addition of navitoclax to ruxolitinib.
To describe the safety profile and PK profile observed with the addition of navitoclax to ruxolitinib.
Participants with documented diagnosis of primary Myelofibrosis, post polycythemia Vera Myelofibrosis or post-essential thrombocythemia myelofibrosis
Participants classified as intermediate-2 or high-risk Myelofibrosis, as defined by the Dynamic International Prognostic Scoring System (DIPSS)
Participant must be ineligible due to age, comorbidities, or unfit for unrelated or unmatched donor transplat, or unwilling to undergo stem cell transplantation at time of study entry
ECOG of 0,1, or 2.
Cohort 1a only: Participants must have received ruxolitinib therapy for at least 12 weeks and be on a stable dose of >/= 10 mg twice daily of ruxolitinib for > Cohort 1b only: Participants must have received prior treatment with ruxolitinib and meet at least one of the criteria outlined per protocol.
Cohort 1b only: Subjects that are receiving ruxolitinib at the time of screening, must currently be on a stable dose ≥ 10 mg twice daily of ruxolitinib for ≥ 4 weeks prior to the 1st dose of navitoclax.
Note: Subjects with ruxolitinib dose reductions within 4 weeks prior to study enrollment are considered to be on stable dose if dose of ruxolitinib is unchanged for > 2 weeks prior to Day 1 of navitoclax. If the dose reduction was due to thrombocytopenia, platelet counts must be confirmed to be stable by a repeat laboratory test.
Cohort 1b only: Subject must not have received treatment with a BET inhibitor or an alternate JAK-2 inhibitor other than ruxolitinib.
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.
Cohort 3 only: Participant must not have received prior treatment with a JAK-2 or BET inhibitor
If female, participant must be either postmenopausal as defined per protocol or practice at least one protocol specified method of birth control starting at Study day 1 through at least 30 days after the last dose of study drug.
Male participants who are sexually active must agree, from study day 1 through at least 30 days after the last dose of study drug, to practice protocol specified contraception.
Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine or serum pregnancy test on Study day 1. Negative pregnancy test must be available prior to first dose.
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.
Participant has a known positive test for HIV
Participant has known hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Participant with an undetectable viral load within 3 months of screening
and those with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate
Ongoing systemic infection (viral, bacterial, or fungal)
Active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, they should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection
Participants positive for active SARS-CoV-2 infection may rescreen after they meet either criteria a or b indicating SARSCoV-2 infection has resolved with viral clearance: At least 14 days since first PCR test result have passed in asymptomatic patients or At least 14 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms.
Cohorts 1b and 3 only: Participant has tested positive for tuberculosis, prior to study entry (subjects must have a negative result per local guidelines prior to study entry)
Participant is concurrently participating in another therapeutic clinical trial or participant has previously participated in other AbbVie clinical trials conducted in participants with myelofibrosis
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