- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04279847
Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (LIMBER)
A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
Study Overview
Status
Conditions
- Myelofibrosis
- Myelodysplastic Syndrome
- Myeloproliferative Neoplasm
- Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome
- Relapsed or Refractory Primary Myelofibrosis
- Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)
- ET (Essential Thrombocythemia)
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Incyte Corporation Call Center (US)
- Phone Number: 1.855.463.3463
- Email: medinfo@incyte.com
Study Contact Backup
- Name: Incyte Corporation Call Center (ex-US)
- Phone Number: 1.855.463.3463
- Email: globalmedinfo@incyte.com
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V6Z2A5
- Recruiting
- St Paul's Hospital
-
-
Ontario
-
Toronto, Ontario, Canada, MG5 2R2
- Recruiting
- Princess Margaret Cancer Center
-
-
-
-
-
Helsinki, Finland, 00029
- Recruiting
- Helsinki University Central Hospital
-
-
-
-
-
Bologna, Italy, 40138
- Recruiting
- L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
-
Firenze, Italy, 50134
- Recruiting
- Azienda Ospedaliero-Universitaria Careggi (Aouc)
-
Meldola, Italy, 47014
- Not yet recruiting
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
-
Milan, Italy, 20122
- Recruiting
- Fondazione Irccs Ca Granda Ospedale Maggiore
-
Orbassano, Italy, 10043
- Not yet recruiting
- Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
-
Verona, Italy, 371134
- Not yet recruiting
- Azienda Ospedaliera Universitaria Integrata Di Verona - Centro Ricerche Cliniche Dr Verona
-
-
-
-
-
Aichi, Japan, 470-1192
- Completed
- Fujita Health University Hospital
-
Chiba, Japan, 277-8577
- Recruiting
- National Cancer Center Hospital East
-
Chiba, Japan, 260-8677
- Recruiting
- Chiba University Hospital
-
Chuo, Japan, 409-3898
- Recruiting
- University of Yamanashi Hospital
-
Fukuoka, Japan
- Completed
- Kyushu University Hospital
-
-
-
-
-
Badalona, Spain, 08916
- Recruiting
- Ico Hospital Germans Trias I Pujol
-
Las Palmas, Spain, 35019
- Recruiting
- Hospital Universitario Insular de Gran Canaria
-
Madrid, Spain, 28041
- Recruiting
- Hospital Universitario 12 de Octubre
-
Murcia, Spain, 30120
- Recruiting
- Hospital Universitario Virgen de la Arrixaca
-
Salamanca, Spain, 37007
- Recruiting
- Hospital Clinico Universitario de Salamanca
-
-
-
-
-
Boston, United Kingdom, PE21 9QS
- Not yet recruiting
- United Lincolnshire Hospitals
-
Manchester, United Kingdom, M20 4BV
- Recruiting
- The Christie Nhs Foundation Trust Uk
-
Oxford, United Kingdom, OX3 7LE
- Recruiting
- University of Oxford
-
-
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- Recruiting
- University of Alabama at Birmingham
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Recruiting
- University of Colorado Cancer Center
-
-
Florida
-
Miami, Florida, United States, 33136
- Recruiting
- University of Miami Sylvester Comprehensive Cancer Center
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University-Winship Cancer Institute
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Not yet recruiting
- Washington University School of Medicine
-
-
New York
-
New York, New York, United States, 10065
- Withdrawn
- Weill Medical College of Cornell University
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27514
- Recruiting
- University of North Carolina at Chapel Hill
-
-
Ohio
-
Cincinnati, Ohio, United States, 45267
- Completed
- University of Cincinnati Cancer Institute
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- MD Anderson Cancer Center
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- Recruiting
- Huntsman Cancer Institute at University of Utah
-
-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Seattle Cancer Care Alliance
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion 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% and no blasts detected/not persistent blast count in peripheral blood at screening or baseline, AND who are currently receiving ruxolitinib and having 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.
Exclusion Criteria:
- 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. Hydroxyurea must be discontinued 3 weeks prior to starting study treatment. 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.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1 : INCB057643 Monotherapy
INCB057643 dose escalation and dose expansion
|
INCB057643 dose escalation and dose expansion.
|
Experimental: Part 2 : INCB057643 Combination with Ruxolitinib
Combination arm in dose escalation and dose expansion
|
INCB057643 dose escalation and dose expansion.
Ruxolitinib will be administered twice a day using the dose described for each Cohort in the protocol for Part 2.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of treatment-emergent adverse events
Time Frame: Up to approximately 9 months
|
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib.
|
Up to approximately 9 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Peripheral Blast Complete Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
|
Defined as peripheral blasts achieving the protocol defined criteria.
|
Up to approximately 9 months
|
Peripheral Blast Partial Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
|
Defined as peripheral blast achieving the protocol defined criteria.
|
Up to approximately 9 months
|
Durable Blast Complete or Partial remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
|
Defined as achieving the protocol defined criteria.
|
Up to approximately 9 months
|
Symptom Response Rate (MF or ET)
Time Frame: Week 24
|
Defined as the proportion of participants who achieve a protocol defined reduction in Total Symptomatic Score (TSS) relative to baseline as measured by the MPN-symptom assessment form (SAF) TSS.
|
Week 24
|
Anemia Response (MF only)
Time Frame: Up to approximately 9 months
|
A hemoglobin increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period during the study treatment period, if transfusion independent (TI) at baseline or Achieving TI for any "rolling" 12-week period during the study treatment period, if transfusion dependent (TD) at baseline.
|
Up to approximately 9 months
|
Duration of Anemia Response (MF only)
Time Frame: Up to approximately 9 months
|
The interval from the first onset of anemia response to the earliest date of loss of anemia response that persists for at least 4 weeks or death from any cause for the TI participants at baseline or duration of RBC-TI period for participants achieving RBC-TI for at least 12 consecutive weeks during the study treatment period for the TD participants at baseline.
|
Up to approximately 9 months
|
Changes in hemoglobin value from baseline (MF only)
Time Frame: Up to approximately 9 months
|
Defined as the mean change from baseline in the hemoglobin value over 12-week treatment periods.
|
Up to approximately 9 months
|
Red Blood Cell (RBC) Transfusion Burden (MF only)
Time Frame: Up to approximately 9 months
|
Defined as the average number of RBC units per participant-month through Weeks 12, 24, and 48.
|
Up to approximately 9 months
|
Overall response (ET only)
Time Frame: Up to approximately 9 months
|
Defined as proportion of participants with complete response or partial response and hematological improvement/response as per definition for ET.
|
Up to approximately 9 months
|
Duration of platelet count reduction or White Blood Cell (WBC) count reduction (ET only)
Time Frame: Up to approximately 9 months
|
Defined as platelet count reduction or WBC count reduction lasting ≥ 12 weeks.
|
Up to approximately 9 months
|
Spleen Volume Response
Time Frame: Week 24
|
Defined as achieving a protocol defined reduction at Week 24 relative to baseline as measured by MRI or CT scan.
|
Week 24
|
Duration of a Spleen Volume Response from baseline (MF only)
Time Frame: Up to approximately 9 months
|
Defined as the interval between the first spleen volume response and the date of the first measurement that no longer achieves the protocol defined criteria.
|
Up to approximately 9 months
|
Bone Marrow (BM) Blast Complete Remission (MF, myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MPN))
Time Frame: Up to approximately 9 months
|
Defined as BM blasts achieving the protocol defined criteria.
|
Up to approximately 9 months
|
BM Blast Partial Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
|
Defined as BM blasts achieving the protocol defined criteria.
|
Up to approximately 9 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Myelofibrosis
- post-essential thrombocythemia myelofibrosis
- myelodysplastic syndrome
- LIMBER
- post-polycythemia vera myelofibrosis
- myeloproliferative neoplasm
- secondary myelofibrosis
- myelodysplastic/myeloproliferative neoplasm overlap syndrome
- BET protein inhibitor
- relapsed primary myelofibrosis
- refractory primary myelofibrosis
- ET (essential thrombocythemia)
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Site
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Precancerous Conditions
- Bone Marrow Neoplasms
- Hematologic Neoplasms
- Neoplasms
- Syndrome
- Myelodysplastic Syndromes
- Primary Myelofibrosis
- Preleukemia
- Thrombocytosis
- Thrombocythemia, Essential
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Polycythemia Vera
- Polycythemia
- Antineoplastic Agents
- INCB057643
Other Study ID Numbers
- INCB 57643-103
- 2023-506145-38-00 (Registry Identifier: EU CT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myelofibrosis
-
Assaf-Harofeh Medical CenterUnknownMyelofibrosis, Primary | Myelofibrosis, Post PV | Myelofibrosis, Post ETIsrael
-
AbbVieRecruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Puerto Rico, Russian Federation, Serbia, South Africa, Spain, Taiwan, ... and more
-
AbbVieActive, not recruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Russian Federation, Serbia, South Africa, Spain, Sweden, Taiwan, Turkey and more
-
AbbVieActive, not recruitingMyelofibrosis (MF)United States, Argentina, Australia, Brazil, Bulgaria, Chile, Hungary, Israel, Italy, Japan, Korea, Republic of, Spain, Sweden, Turkey
-
AbbVieTerminatedMyelofibrosis (MF)United States, Korea, Republic of, South Africa
-
Centre Hospitalier Annecy GenevoisCompleted
-
National Taiwan University HospitalRecruitingPre-fibrotic MyelofibrosisTaiwan
-
The University of Hong KongRecruitingMyelofibrosis | Primary Myelofibrosis, Prefibrotic StageHong Kong
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.RecruitingModerate and High Risk MyelofibrosisChina
-
Novartis PharmaceuticalsTerminatedMyelofibrosis With High Molecular Risk MutationsBelgium, Spain, United Kingdom, Hungary, Italy, Japan, Taiwan, Germany, Canada, Singapore, Austria, Australia, France, Israel, Sweden, Switzerland, Hong Kong, Greece, Turkey, Brazil, Russian Federation, Denmark, Portugal, Norway, Poland
Clinical Trials on INCB057643
-
Incyte CorporationTerminatedMetastatic Cancer | Solid Tumors | Advanced MalignanciesUnited States, United Kingdom, Spain
-
Incyte CorporationTerminatedSolid TumorsUnited States, Belgium, France