A Study Evaluating Safety and Tolerability and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm

  • STATUS
    Recruiting
  • End date
    Jan 12, 2025
  • participants needed
    62
  • sponsor
    AbbVie
Updated on 1 September 2021
stem cell transplantation
myelofibrosis
chronic myelomonocytic leukemia
ruxolitinib
leukemia
bone marrow procedure
polycythemia vera
essential thrombocythemia
thrombocytosis
polycythemia

Summary

www.myelofibrosisresearch.com


There are 4 parts to this study for which the primary objectives are to evaluate safety, tolerability, and pharmacokinetics (PK) of navitoclax when administered alone (Part 1) or when administered in combination with ruxolitinib (Part 2). In Part 2, participants must have been receiving a stable dose of ruxolitinib therapy for at least 12 weeks prior to study enrollment. In Part 3, all eligible participants will receive navitoclax, with the primary objective being to evaluate potential navitoclax effect on QTc prolongation. In Part 4, effect of navitoclax is evaluated on the PK, safety, and tolerability of a single dose of celecoxib in participants with myeloproliferative neoplasm (MPN) or chronic myelomonocytic leukemia (CMML).

Description


Details
Condition MYELOPROLIFERATIVE DISORDER, Myeloproliferative Neoplasms, myeloproliferative neoplasm, myeloproliferative disorders
Treatment Celecoxib, Ruxolitinib, Navitoclax
Clinical Study IdentifierNCT04041050
SponsorAbbVie
Last Modified on1 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Parts 1 and 2
Navitoclax Monotherapy (Part 1 Only - Japanese Participants)
Documented diagnosis of myelofibrosis (MF), polycythemia vera (PV) or essential thrombocythemia (ET) as defined by the World Health Organization (WHO) classification
MF participants must have received and failed or are intolerant to ruxolitinib therapy
ET or PV participants 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 Only - Japanese and Taiwanese Participants)
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 (WHO) 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 >= 50 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 of ruxolitinib (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 for participants with ET and PV therapy within 14 days prior to the first dose of navitoclax will be allowed pending additional discussion with study doctor. Ruxolitinib for MF participants will not be allowed within 7 days prior to the first dose of study drug and during navitoclax administration
Eastern Cooperative Oncology Group (ECOG) performance status <= 1
Part 3 and Part 4 (Participants in US and Europe)
Part 3 Only: At screening or baseline (pre-dose on Day 1), participant has QT interval corrected for heart rate (QTc) interval by Fridericia's correction (QTcF) <= 470 msec
Participants with a documented diagnosis of primary or secondary MF, ET, PV or chronic myelomonocytic leukemia (CMML) as defined by the WHO classification
Participants must be requiring treatment and have failed or are intolerant to at least one prior therapy or who refuse standard therapy
ECOG performance status <= 2
Must have adequate bone marrow, kidney, liver and hematology blood values as detailed in the study protocol

Exclusion Criteria

Part 1 and 2
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 (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and low-molecular-weight heparin (LMWH)
Has received strong or moderate CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 14 days prior to the administration of the first dose of navitoclax
Part 3 and Part 4
Had prior therapy with a BH3 mimetic compound
Have received strong or moderate CYP3A inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of navitoclax
Have received strong CYP3A inducers within 10 days prior to the first dose of navitoclax
Show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy)
Currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH
Part 4 Only
Have received CYP2C9 inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs
Have received CYP2C9 inducers within 10 days prior to the first dose of study drugs
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