Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (LIMBER)
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| ClinicalTrials.gov Identifier: NCT04279847 |
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Recruitment Status :
Recruiting
First Posted : February 21, 2020
Last Update Posted : June 2, 2023
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Sponsor:
Incyte Corporation
Information provided by (Responsible Party):
Incyte Corporation
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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) | Drug: INCB057643 Drug: Ruxolitinib | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 138 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | monotherapy and ruxoltinib combination |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms |
| Actual Study Start Date : | February 23, 2021 |
| Estimated Primary Completion Date : | November 11, 2024 |
| Estimated Study Completion Date : | November 11, 2024 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Ruxolitinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1 : INCB057643 Monotherapy
INCB057643 dose escalation and dose expansion
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Drug: INCB057643
INCB057643 dose escalation and dose expansion. |
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Experimental: Part 2 : INCB057643 Combination with Ruxolitinib
Combination arm in dose escalation and dose expansion
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Drug: INCB057643
INCB057643 dose escalation and dose expansion. Drug: Ruxolitinib 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 Measures :
- 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.
Secondary Outcome Measures :
- Overall Response Rate [ Time Frame: up to approximately 9 months ]Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
- Symptom Response Rate [ 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-SAF TSS
- Anemia response [ Time Frame: Up to approximately 9 months ]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 [ 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 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 [ Time Frame: 24 and 48 Weeks ]Defined as the average number of RBC units per participant month
- Percentage change in Spleen Volume [ Time Frame: 12 and 24 weeks ]Defined as percentage of participants with a protocol defined Spleen Volume Reduction (SVR)
- Spleen length response [ Time Frame: Up to approximately 9 months ]Defined as the proportion of participants achieving a protocol defined reduction in spleen length at any visit relative to baseline as measured by palpation
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 18 years and older at the time of signing the informed consent.
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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).
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MDS
- Very low-, low-, intermediate-, or high risk MDS as per the IPSS-R criteria
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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.
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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.
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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:
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04279847
Contacts
| Contact: Incyte Corporation Call Center (US) | 1.855.463.3463 | medinfo@incyte.com | |
| Contact: Incyte Corporation Call Center (ex-US) | 1.855.463.3463 | globalmedinfo@incyte.com |
Locations
Show 27 study locations
Sponsors and Collaborators
Incyte Corporation
Additional Information:
| Responsible Party: | Incyte Corporation |
| ClinicalTrials.gov Identifier: | NCT04279847 |
| Other Study ID Numbers: |
INCB 57643-103 |
| First Posted: | February 21, 2020 Key Record Dates |
| Last Update Posted: | June 2, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Access to patient level data is not available for this study |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Incyte Corporation:
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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 |
Additional relevant MeSH terms:
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Neoplasms Preleukemia Polycythemia Vera Myelodysplastic Syndromes Primary Myelofibrosis Myeloproliferative Disorders Polycythemia Thrombocytosis Thrombocythemia, Essential Myelodysplastic-Myeloproliferative Diseases Syndrome Disease |
Pathologic Processes Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Bone Marrow Neoplasms Hematologic Neoplasms Neoplasms by Site Blood Platelet Disorders Blood Coagulation Disorders Hemorrhagic Disorders INCB057643 Antineoplastic Agents |