A Phase 1/2 Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders
- Conditions
- Anaemia associated with myelofibrosis whether as a de novo disorder (PMF) or evolve secondarily from previous PV or ET (post–PV MF or post–ET MF).MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10074689Term: Post polycythemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10074690Term: Post essential thrombocythemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10074691Term: Post polycythaemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10074692Term: Post essential thrombocythaemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10077161Term: Primary myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004029-21-FR
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 100
1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Age 18 years or older at the time of signing the ICF.
3. ECOG performance status score of the following:
a. 0 or 1 for the dose-escalation stages.
b. 0, 1, or 2 for the dose-expansion stage.
4. Life expectancy is greater than 6 months.
5. Agreement to undergo a pretreatment and regular on-study BM biopsies and aspirates (as
appropriate to disease).
6. Agreement to avoid pregnancy or fathering children based on the criteria below:
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 study treatment
dose and must refrain from donating sperm during this period.
b. Women of childbearing potential must have a negative serum pregnancy test at
screening before the first dose and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period
c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or
bilateral oophorectomy OR = 12 months of amenorrhea and at least 50 years of age)
are eligible.
7. Participants with MF who are transfusion-dependent or present with symptomatic
anemia, defined as follows:
a. Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on
3 separate occasions with at least 7 days between measurements
b. Transfusion-dependent: Participant has received at least 4 units of RBC transfusions
during the 28 days immediately preceding Cycle 1 Day 1 OR has received at least
4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for
an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia.
In addition, the most recent transfusion episode must have occurred in the 28 days
before Cycle 1 Day 1.
8. Histologically confirmed diagnosis of PMF, post-PV, or post-ET MF according to the 2016 WHO criteria.
9. Ineligible to receive or have not responded to available therapies for anemia such as
ESAs.
10. Participants with BM and peripheral blood myeloblast count < 10%.
For TGA:
11. Participants previously treated with JAK inhibitors (intolerant, resistant, refractory, or
lost response to a JAK inhibitor) for at least 12 weeks.
12. Participants with intermediate-2 or high DIPSS MF (according to IWG-MRT criteria).
For TGB:
13. Participants must have been on a therapeutic and stable regimen of ruxolitinib (ie, the
dose and dose-regimen of ruxolitinib to treat the MF has not been modified at any time)
for at least 12 consecutive weeks immediately preceding the first dose of study treatment.
14. Participants with intermediate-1, intermediate-2, or high DIPSS MF (according to
IWG-MRT criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Undergone any prior allogenic or autologous stem cell transplantation or a candidate for
such transplantation.
2. Any major surgery within 28 days before the first dose of study treatment.
3. Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy,
biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating
agent to treat the participant's disease, with the exception of ruxolitinib for TGB only,
within 5 half-lives or 28 days (whichever is shorter) before the first dose of study
treatment.
4. Undergoing treatment with another investigational medication or having been treated
with an investigational medication within 28 days before the first dose of study treatment.
5. Undergoing treatment with a potent/strong inhibitor or inducer of CYP3A4/5 within
28 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or
expected to receive such treatment during the study.
6. Any prior radiation therapy within 28 days before the first dose of study treatment.
7. Presence of any hematological malignancy other than PMF, post-PV, or post-ET MF, as
applicable.
8. Active invasive malignancy over the previous 5 years.
9. Known active disease involving the CNS.
10. History of clinically significant or uncontrolled cardiac disease, including recent (within
the last 12 months) unstable angina or acute myocardial infarction, or New York Heart
Association Class III or IV congestive heart failure, or clinically significant arrhythmias
not controlled by medication.
11. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically
meaningful.
12. Presence of chronic or current active infectious disease requiring systemic antibiotic,
antifungal, or antiviral treatment.
13. Participants with diagnosis of chronic liver disease
14. Participants with known active hepatitis A, HBV, or HCV infection or who are HIV-positive.
15. Unwillingness to be transfused with blood components including RBC packs and platelet
transfusions.
16. Any condition in the investigator's judgment that would interfere with full participation in
the study.
17. Active alcohol or drug addiction that would interfere with their ability to comply with the
study requirements.
18. Gastroesophageal reflux disease not controlled by medication within 28 days before the first dose of study treatment.
19. Has any unresolved toxicity = Grade 2 from previous therapy except for stable chronic
toxicities (= Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
20. Known hypersensitivity, severe reaction, or any known contraindications to the use of
any of the active substances or excipients in INCB000928 or ruxolitinib as appropriate to
the relevant treatment group.
21. Women who are pregnant or breastfeeding.
22. Unable to swallow and retain oral medication.
23. Current use of prohibited medication
24. Participants with laboratory values at screening as defined.
25. Participants undergoing treatment with ESAs, G-CSF or GM-CSF, romiplostin, or
eltrombopag at any time within 4 weeks before the first dose of study treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method