ACTIVE_NOT_RECRUITING

Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms

Conditions

Myelofibrosis Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome Myeloproliferative Neoplasm Relapsed or Refractory Primary Myelofibrosis Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)ET (Essential Thrombocythemia)BET protein inhibitor relapsed primary myelofibrosis refractory primary myelofibrosis secondary myelofibrosis post-polycythemia vera myelofibrosis post-essential thrombocythemia myelofibrosis LIMBER

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of INCB057643 as monotherapy or combination with ruxolitinib for participants with myelofibrosis (MF) and other myeloid neoplasms.

Official Title

A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms

Quick Facts

Study Start:2021-02-23

Study Completion:2026-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04279847

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age 18 years and older at the time of signing the informed consent. * Part 1 Monotherapy: Participants with confirmed diagnosis of relapsed or refractory MF (primary, or post-PV and post-ET), MDS, MDS/MPN, or ET who have received at least 1 prior line of therapy; are either refractory, relapsed, or intolerant to the last therapy; and there is no available therapy that would provide clinical benefit in the opinion of the investigator. * a. MF with measurable disease (palpable spleen and symptoms) as defined in the protocol and risk category of intermediate 2 or high according to DIPSS. MF participants must have received a JAK inhibitor(s), such as ruxolitinib. * b. ET participants should have disease refractory to hydroxyurea as defined by the protocol. * Part 2 Combination with ruxolitinib. * a. Primary MF or secondary MFs (post-PV MF and post-ET MF), histologically or cytologically confirmed, with measurable disease (palpable spleen and symptoms) as defined in the protocol, either currently receiving ruxolitinib with suboptimal response or JAKi-naive. * b. Suboptimal response is defined as currently being treated with ruxolitinib monotherapy at a stable dose for ≥ 8 weeks immediately preceding the first dose of study treatment. One dose reduction due to toxicities within 8 weeks prior to Study Day 1 is permitted. * c. JAKi-naive is defined as those participants that have no prior use of any JAK inhibitor, including ruxolitinib, and; * d. Part 2 dose escalation: Risk category of intermediate-2 or high according to DIPSS. * e. Part 2 dose expansion: Risk category of intermediate-1, intermediate-2, or high according to DIPSS. * f. Part 2 dose expansion participants with chronic MF are defined as participants with bone marrow myeloblast percentage \< 5% (not applicable if dry tap or blast count deemed not reliable by the investigator) and blast count in peripheral blood \< 1% at screening and who are currently receiving ruxolitinib and having a suboptimal response. * g. Part 2 dose expansion participants with accelerated-phase MF are defined as having either a bone marrow myeloblast percentage ≥ 5% to \< 20% or a myeloblast percentage ≥ 10% in peripheral blood on 2 occasions at least 2 weeks apart, AND are currently receiving ruxolitinib and have a suboptimal response. * h. Part 2 dose expansion participants with JAKi-naive MF are eligible to receive ruxolitinib, with peripheral blood blast count of \< 10% at the screening hematology assessment. * Must not be a candidate for potentially curative therapy, including hematopoietic stem cell transplantation. * ECOG performance status 0 to 2. * Life expectancy ≥ 24 weeks. * Willingness to avoid pregnancy or fathering children based on criteria. * a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. * b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. * c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea without any other medical reasons such as treatment with anticancer agents) are eligible.	* Prior receipt of a BET inhibitor. * Receipt of anticancer medications or investigational drugs within the protocol-defined interval before the first dose of study treatment. For Part 2 JAKi-naive, prior use of a JAK inhibitor (including ruxolitinib) and no use of experimental drug therapy for MF or any other standard drug (except hydroxyurea) used for MF or another indication within 3 months of starting study drug. For participants with suboptimal response to ruxolitinib, ruxolitinib will continue at the participants' current ongoing doses, no ruxolitinib washout is needed. * Participants with exclusionary laboratory values at screening defined as, including, but not limited to, * a. Platelets. Part 1 (monotherapy dose expansion, MF): \< 75 × 109/L. Part 1 (monotherapy dose expansion, ET): \< 450 × 109/L. Part 2 (combination dose escalation and expansion): \< 75 × 109/L. Part 2 (combination dose expansion, JAKi-naïve MF): \< 100 × 109/L. * b. Hemoglobin: Participants unwilling to receive red blood cell transfusion to treat low hemoglobin levels are excluded. * c. ANC \< 0.75 × 109/L. * inadequate renal, hepatic and coagulation functions as defined in the protocol. * Concurrent anticancer therapy other than the therapies being tested in this study. * Participants who have received allogeneic hematopoietic stem cell transplantation within 6 months of enrollment (unless approved by the medical monitor), or have active graft versus-host disease, or have received immunosuppressive therapy following allogeneic transplant within 2 weeks of the first dose of study treatment. * Unless approved by the medical monitor, may not have received autologous hematopoietic stem-cell transplant within 3 months before the first dose of study treatment. * Significant concurrent, uncontrolled medical condition, including but not limited to, significant GI disorder, history of or current clinically significant or uncontrolled cardiac disease, history or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful, and history of bleeding disorder or at a high risk of bleeding. * Active bacterial, fungal, parasitic, or viral infection that requires therapy. * Current use of prohibited medication as described in the protocol, including the use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment.

Inclusion Criteria

Exclusion Criteria

* Age 18 years and older at the time of signing the informed consent.
* Part 1 Monotherapy: Participants with confirmed diagnosis of relapsed or refractory MF (primary, or post-PV and post-ET), MDS, MDS/MPN, or ET who have received at least 1 prior line of therapy; are either refractory, relapsed, or intolerant to the last therapy; and there is no available therapy that would provide clinical benefit in the opinion of the investigator.
* a. MF with measurable disease (palpable spleen and symptoms) as defined in the protocol and risk category of intermediate 2 or high according to DIPSS. MF participants must have received a JAK inhibitor(s), such as ruxolitinib.
* b. ET participants should have disease refractory to hydroxyurea as defined by the protocol.
* Part 2 Combination with ruxolitinib.
* a. Primary MF or secondary MFs (post-PV MF and post-ET MF), histologically or cytologically confirmed, with measurable disease (palpable spleen and symptoms) as defined in the protocol, either currently receiving ruxolitinib with suboptimal response or JAKi-naive.
* b. Suboptimal response is defined as currently being treated with ruxolitinib monotherapy at a stable dose for ≥ 8 weeks immediately preceding the first dose of study treatment. One dose reduction due to toxicities within 8 weeks prior to Study Day 1 is permitted.
* c. JAKi-naive is defined as those participants that have no prior use of any JAK inhibitor, including ruxolitinib, and;
* d. Part 2 dose escalation: Risk category of intermediate-2 or high according to DIPSS.
* e. Part 2 dose expansion: Risk category of intermediate-1, intermediate-2, or high according to DIPSS.
* f. Part 2 dose expansion participants with chronic MF are defined as participants with bone marrow myeloblast percentage \< 5% (not applicable if dry tap or blast count deemed not reliable by the investigator) and blast count in peripheral blood \< 1% at screening and who are currently receiving ruxolitinib and having a suboptimal response.
* g. Part 2 dose expansion participants with accelerated-phase MF are defined as having either a bone marrow myeloblast percentage ≥ 5% to \< 20% or a myeloblast percentage ≥ 10% in peripheral blood on 2 occasions at least 2 weeks apart, AND are currently receiving ruxolitinib and have a suboptimal response.
* h. Part 2 dose expansion participants with JAKi-naive MF are eligible to receive ruxolitinib, with peripheral blood blast count of \< 10% at the screening hematology assessment.
* Must not be a candidate for potentially curative therapy, including hematopoietic stem cell transplantation.
* ECOG performance status 0 to 2.
* Life expectancy ≥ 24 weeks.
* Willingness to avoid pregnancy or fathering children based on criteria.
* a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
* b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
* c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea without any other medical reasons such as treatment with anticancer agents) are eligible.

* Prior receipt of a BET inhibitor.
* Receipt of anticancer medications or investigational drugs within the protocol-defined interval before the first dose of study treatment. For Part 2 JAKi-naive, prior use of a JAK inhibitor (including ruxolitinib) and no use of experimental drug therapy for MF or any other standard drug (except hydroxyurea) used for MF or another indication within 3 months of starting study drug. For participants with suboptimal response to ruxolitinib, ruxolitinib will continue at the participants' current ongoing doses, no ruxolitinib washout is needed.
* Participants with exclusionary laboratory values at screening defined as, including, but not limited to,
* a. Platelets. Part 1 (monotherapy dose expansion, MF): \< 75 × 109/L. Part 1 (monotherapy dose expansion, ET): \< 450 × 109/L. Part 2 (combination dose escalation and expansion): \< 75 × 109/L. Part 2 (combination dose expansion, JAKi-naïve MF): \< 100 × 109/L.
* b. Hemoglobin: Participants unwilling to receive red blood cell transfusion to treat low hemoglobin levels are excluded.
* c. ANC \< 0.75 × 109/L.
* inadequate renal, hepatic and coagulation functions as defined in the protocol.
* Concurrent anticancer therapy other than the therapies being tested in this study.
* Participants who have received allogeneic hematopoietic stem cell transplantation within 6 months of enrollment (unless approved by the medical monitor), or have active graft versus-host disease, or have received immunosuppressive therapy following allogeneic transplant within 2 weeks of the first dose of study treatment.
* Unless approved by the medical monitor, may not have received autologous hematopoietic stem-cell transplant within 3 months before the first dose of study treatment.
* Significant concurrent, uncontrolled medical condition, including but not limited to, significant GI disorder, history of or current clinically significant or uncontrolled cardiac disease, history or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful, and history of bleeding disorder or at a high risk of bleeding.
* Active bacterial, fungal, parasitic, or viral infection that requires therapy.
* Current use of prohibited medication as described in the protocol, including the use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment.

Contacts and Locations

Study Locations (Sites)

University of Alabama At Birmingham

Birmingham, Alabama, 35294

United States

University of Colorado Cancer Center

Aurora, Colorado, 80045

United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

United States

Emory University-Winship Cancer Institute

Atlanta, Georgia, 30322

United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Rutgers Cancer Institute of Nj

New Brunswick, New Jersey, 08901

United States

Nyu Langone Health - Long Island Hospital

Mineola, New York, 11501

United States

Nyu Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016

United States

Weill Medical College of Cornell University

New York, New York, 10021

United States

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27514

United States

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267

United States

Ohio State University

Columbus, Ohio, 43210

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, 75246

United States

Md Anderson Cancer Center

Houston, Texas, 77030

United States

Oncology Consultants

Houston, Texas, 77030

United States

Huntsman Cancer Institute At University of Utah

Salt Lake City, Utah, 84112

United States

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Incyte Corporation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-23

Study Completion Date2026-12-30

Study Record Updates

Study Start Date2021-02-23

Study Completion Date2026-12-30

Terms related to this study

Keywords Provided by Researchers

Myelofibrosis
myelodysplastic syndrome
myelodysplastic/myeloproliferative neoplasm overlap syndrome
myeloproliferative neoplasm
BET protein inhibitor
relapsed primary myelofibrosis
refractory primary myelofibrosis
secondary myelofibrosis
post-polycythemia vera myelofibrosis
post-essential thrombocythemia myelofibrosis
LIMBER
ET (essential thrombocythemia)

Additional Relevant MeSH Terms

Myelofibrosis
Myelodysplastic Syndrome
Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome
Myeloproliferative Neoplasm
Relapsed or Refractory Primary Myelofibrosis
Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)
ET (Essential Thrombocythemia)