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

Primary Purpose

Myelofibrosis, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INCB057643
Ruxolitinib
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Relapsed or refractory primary myelofibrosis (MF), secondary MFs (post-polycythemia vera MF, post- essential thrombocythemia MF) myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), and myelodysplastic/myeloproliferative neoplasm overlap syndrome (MDS/MPN)
  • Must not be a candidate for potentially curative therapy, including hematopoietic stem-cell transplantation.
  • Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate at screening/baseline, or archival sample obtained since completion of most recent therapy.
  • Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

  • Prior receipt of a BET inhibitor within 5 half-lives of the compound, and/or experienced BET inhibitor-related AE(s) resulting in dose discontinuation.
  • Receipt of anticancer medications or investigational drugs within the protocol-defined interval before the first dose of study treatment:

Note: For participants in Part 2, Treatment Group B, ruxolitinib will continue at the participants' current, ongoing doses. No ruxolitinib washout is needed.

Sites / Locations

  • University of Alabama At BirminghamRecruiting
  • University of Colorado Cancer CenterRecruiting
  • University of Miami Sylvester Comprehensive Cancer CenterRecruiting
  • Emory University-Winship Cancer InstituteRecruiting
  • University of North Carolina At Chapel HillRecruiting
  • University of Cincinnati Cancer Institute
  • Md Anderson Cancer CenterRecruiting
  • Huntsman Cancer Institute At University of UtahRecruiting
  • Seattle Cancer Care AllianceRecruiting
  • St Paul'S HospitalRecruiting
  • Princess Margaret Cancer CenterRecruiting
  • Helsinki University Central HospitalRecruiting
  • L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - MalpighiRecruiting
  • Azienda Ospedaliero-Universitaria Careggi (Aouc)Recruiting
  • Fondazione Irccs Ca Granda Ospedale MaggioreRecruiting
  • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
  • Azienda Ospedaliera Universitaria Integrata Di Verona - Centro Ricerche Cliniche Dr Verona
  • Fujita Health University Hospital
  • Chiba University HospitalRecruiting
  • National Cancer Center Hospital EastRecruiting
  • University of Yamanashi HospitalRecruiting
  • Kyushu University Hospital
  • Ico Hospital Germans Trias I PujolRecruiting
  • Hospital Universitario Insular de Gran CanariaRecruiting
  • Hospital Universitario 12 de OctubreRecruiting
  • Hospital Universitario Virgen de La ArrixacaRecruiting
  • Hospital Clinico Universitario de SalamancaRecruiting
  • United Lincolnshire Hospitals
  • The Christie Nhs Foundation Trust UkRecruiting
  • University of OxfordRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1 : INCB057643 Monotherapy

Part 2 : INCB057643 Combination with Ruxolitinib

Arm Description

INCB057643 dose escalation and dose expansion

Combination arm in dose escalation and dose expansion

Outcomes

Primary Outcome Measures

Number of treatment-emergent adverse events
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.

Secondary Outcome Measures

Overall Response Rate
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Symptom Response Rate
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-SAF TSS
Anemia response
Hemoglobin increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period during the first 24 weeks of treatment, if Transfusion Independent (TI) at baseline or achieving TI for any rolling 12 week period during the first 24 weeks of treatment if Transfusion Dependent (TD) at baseline
Duration of Anemia Response
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 first 24 weeks of treatment for the TD participants at baseline, or Mean change from baseline in the hemoglobin value over 12-week treatment periods
Rate of red blood cell (RBC) transfusion dependency
Defined as the average number of RBC units per participant month
Percentage change in Spleen Volume
Defined as percentage of participants with a protocol defined Spleen Volume Reduction (SVR)
Spleen length response
Defined as the proportion of participants achieving a protocol defined reduction in spleen length at any visit relative to baseline as measured by palpation

Full Information

First Posted
February 18, 2020
Last Updated
September 27, 2023
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04279847
Brief Title
Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
Acronym
LIMBER
Official Title
A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2021 (Actual)
Primary Completion Date
November 11, 2024 (Anticipated)
Study Completion Date
November 11, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 and other myeloid neoplasms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
monotherapy and ruxoltinib combination
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
138 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 : INCB057643 Monotherapy
Arm Type
Experimental
Arm Description
INCB057643 dose escalation and dose expansion
Arm Title
Part 2 : INCB057643 Combination with Ruxolitinib
Arm Type
Experimental
Arm Description
Combination arm in dose escalation and dose expansion
Intervention Type
Drug
Intervention Name(s)
INCB057643
Intervention Description
INCB057643 dose escalation and dose expansion.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
Ruxolitinib will be administered twice a day using the dose designated as the stable dose at the time of the screening visit for each subject. Acceptable doses are 5 mg BID to 25 mg BID.
Primary Outcome Measure Information:
Title
Number of treatment-emergent adverse events
Description
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.
Time Frame
Up to approximately 9 months
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Time Frame
up to approximately 9 months
Title
Symptom Response Rate
Description
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-SAF TSS
Time Frame
Week 24
Title
Anemia response
Description
Hemoglobin increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period during the first 24 weeks of treatment, if Transfusion Independent (TI) at baseline or achieving TI for any rolling 12 week period during the first 24 weeks of treatment if Transfusion Dependent (TD) at baseline
Time Frame
Up to approximately 9 months
Title
Duration of Anemia Response
Description
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 first 24 weeks of treatment for the TD participants at baseline, or Mean change from baseline in the hemoglobin value over 12-week treatment periods
Time Frame
Up to approximately 9 months
Title
Rate of red blood cell (RBC) transfusion dependency
Description
Defined as the average number of RBC units per participant month
Time Frame
24 and 48 Weeks
Title
Percentage change in Spleen Volume
Description
Defined as percentage of participants with a protocol defined Spleen Volume Reduction (SVR)
Time Frame
12 and 24 weeks
Title
Spleen length response
Description
Defined as the proportion of participants achieving a protocol defined reduction in spleen length at any visit relative to baseline as measured by palpation
Time Frame
Up to approximately 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years and older at the time of signing the informed consent. Part 1: Relapsed or refractory MF, MDS, or MDS/MPN a. Disease type: •MF Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or cytologically confirmed according to WHO 2016 criteria with measurable disease and risk category of intermediate-2 or high according to DIPSS. Measurable disease is defined: For dose escalation as having a palpable spleen of ≥ 5 cm below the left subcostal margin (ribs). MDS Very low-, low-, intermediate-, or high risk MDS as per the IPSS-R criteria MDS/MPN Low-, intermediate-, or high-risk chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis, and MDS/MPN unclassifiable as per the WHO 2016 criteria. Exception: Participants presenting with juvenile myelomonocytic leukemia will be excluded. b. Prior therapy Received at least 1 line of prior therapy; is refractory, relapsed, or intolerant to the last therapy; and there is no further available therapy known to provide clinical benefits, in the opinion of the investigator. Participants with MF must have received a JAK inhibitor(s) such as ruxolitinib. Part 2: MF - dose escalation and expansion a. Disease type Primary MF or secondary MFs (post-PV MF, post-ET MF), histologically or cytologically confirmed according to WHO 2016 criteria. Measurable disease is defined as having a palpable spleen of > 10 cm below the left subcostal margin. 2 subgroups of participants in Part 2 - dose expansion will be enrolled: bone marrow myeloblast percentage between 5% (≥ 5%) and less than 20% (< 20%) or myeloblast percentage ≥ 10% in peripheral blood in 2 occasions at least 2 weeks apart. b. Prior therapy Must currently be treated with ruxolitinib monotherapy at a stable dose for ≥ 8 weeks immediately preceding the first dose of study treatment. Must not be a candidate for potentially curative therapy, including hematopoietic stem-cell transplantation. Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate at screening/baseline, or archival sample obtained since completion of most recent therapy. Willingness to avoid pregnancy or fathering children based on the criteria below. Exclusion Criteria: Prior receipt of a BET inhibitor within 5 half-lives of the compound, and/or experienced BET inhibitor-related AE(s) resulting in dose discontinuation. Note: For participants in Part 2, ruxolitinib will continue at the participants' current, ongoing doses. No ruxolitinib washout is needed. Concurrent anticancer therapy Participants who have received allogeneic hematopoietic stem cell transplantation within 6 months of enrollment Active HBV or HCV infection or at risk for HBV reactivation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Incyte Corporation Call Center (US)
Phone
1.855.463.3463
Email
medinfo@incyte.com
First Name & Middle Initial & Last Name or Official Title & Degree
Incyte Corporation Call Center (ex-US)
Phone
1.855.463.3463
Email
globalmedinfo@incyte.com
Facility Information:
Facility Name
University of Alabama At Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Emory University-Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
University of North Carolina At Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Completed
Facility Name
Md Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Huntsman Cancer Institute At University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
St Paul'S Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z2A5
Country
Canada
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
MG5 2R2
Country
Canada
Individual Site Status
Recruiting
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Individual Site Status
Recruiting
Facility Name
L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Ospedaliero-Universitaria Careggi (Aouc)
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione Irccs Ca Granda Ospedale Maggiore
City
Milan
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
Azienda Ospedaliera Universitaria Integrata Di Verona - Centro Ricerche Cliniche Dr Verona
City
Verona
ZIP/Postal Code
371134
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
Fujita Health University Hospital
City
Aichi
ZIP/Postal Code
470-1192
Country
Japan
Individual Site Status
Completed
Facility Name
Chiba University Hospital
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Cancer Center Hospital East
City
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
University of Yamanashi Hospital
City
Chuo
ZIP/Postal Code
409-3898
Country
Japan
Individual Site Status
Recruiting
Facility Name
Kyushu University Hospital
City
Fukuoka
Country
Japan
Individual Site Status
Completed
Facility Name
Ico Hospital Germans Trias I Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Insular de Gran Canaria
City
Las Palmas
ZIP/Postal Code
35019
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen de La Arrixaca
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Clinico Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Name
United Lincolnshire Hospitals
City
Boston
ZIP/Postal Code
PE21 9QS
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
The Christie Nhs Foundation Trust Uk
City
Manchester
ZIP/Postal Code
M20 4BV
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University of Oxford
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Access to patient level data is not available for this study
Links:
URL
https://www.incyteclinicaltrials.com/limber/
Description
Related Info

Learn more about this trial

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

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