A Phase 2, Open-Label, Monotherapy, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement
The goal of this clinical research study is to learn if INCB054828 can help to control myeloproliferative or lymphoproliferative neoplasm (a type of blood cancer) in patients who also have a type of genetic mutation (change) called 8p11. The safety and tolerability of INCB054828 will also be studied.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: INCB054828
Treatment Location: Both at MDACC & and Other Sites
Primary Objective: The primary objective of this study is to evaluate the efficacy of INCB054828 in subjects with myeloid/lymphoid neoplasms with fibroblast growth factor receptor (FGFR) 1 rearrangement. Secondary Objective: The secondary objective is to evaluate the safety of INCB054828 in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement. Exploratory Objective: Additional exploratory objectives are to evaluate pharmacokinetics (PK), biomarkers, and quality of life of subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement treated with INCB054828.
IRB Review and Approval Date: 03/14/2017
Recruitment Status: Open
Projected Accrual: 46
1) Men and women, aged 18 or older.
2) Documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, based on standard diagnostic cytogenetic evaluation performed locally, before signing informed consent for this study.
3) Only subjects who are not candidates for stem cell transplantation or have relapsed after stem cell transplantation and delayed lymphocyte infusion and who have progressed and are not candidates for other disease-modifying therapies are eligible for the study. All relapsed/refractory subjects must have evidence of either cytogenetic or hematological disease and have no evidence of residual toxicity (e.g., graft-versus-host disease requiring treatment).
4) Life expectancy equal to or more than 12 weeks.
5) ECOG performance status 0 to 2
6) Willingness to avoid pregnancy or fathering children based on the following: a. Woman of non childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR equal to or 12 months of amenorrhea). b. Woman of childbearing potential who has a negative pregnancy test at screening and before the first dose on Day 1 and who agrees 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 subject and their understanding confirmed. A follow-up pregnancy test will be performed at EOT visit. c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after last dose. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.
1) Treatment with other investigational study drug for any indication
for any reason, or receipt of antineoplastic medications within 21 days
or 5 half-lives (whichever is longer) before first dose of study drug.
For biologic therapies, last treatment must have been within 28 days
before the first dose of study drug. Subjects must have recovered (Grade
equal to or less than 1 or at pretreatment baseline) from AEs from
previously administered therapies. Hydroxyurea and low-dose steroids
(equivalent to prednisone 20 mg per day) are permitted up to 24 hours
before the first dose.
2) Prior receipt of a selective FGFR inhibitor.
3) Untreated brain or central nervous system (CNS) involvement that has progressed (eg, evidence of new neurological symptoms attributable to brain/CNS involvement). Subjects with previously treated and clinically stable brain/CNS disease and who are off all corticosteroids for equal to or more than 4 weeks are eligible.
4) Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy that has undergone potentially curative therapy.
5) Have abnormal laboratory parameters: a. Total bilirubin equal to or more than 1.5 × upper limit of normal (ULN; equal to or more than 2.5 × ULN if Gilbert syndrome or disease involving liver). b. AST and ALT > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver involvement). c. Creatinine clearance equal to or less than 30 mL/min based on Cockroft-Gault. d. Serum phosphate > institutional ULN. e. Serum calcium outside of the institutional normal range, or serum albumin–correct calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range.
6) History of human immunodeficiency virus infection.
7) Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
8) History or presence of an abnormal ECG that in the investigator's opinion is clinically meaningful.
9) History of clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or arrhythmia requiring therapy. Subjects with a pacemaker and well-controlled rhythm for at least 1 month before the first dose will be allowed.
10) Have undergone major surgical procedure other than for diagnosis within 28 days before Cycle 1 Day 1.
11) Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
12) Pregnant or nursing women or subjects expecting to conceive or father children within the projected duration of the study, starting with the screening visit through completion of safety follow-up visit (90 days from date of last dose for male subjects).
13) Concurrent antineoplastic therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, or investigational therapy).
14) History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification.
15) Current evidence of corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjuctivitis, as confirmed by ophthalmologic examination.
16) Current use of prohibited medication.
17) Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug.
18) Known hypersensitivity or severe reaction to INCB054828 or excipients of INCB054828 study drug
19) Inability or unlikeliness to comply with the dose schedule and study evaluations, in the opinion of the investigator.
20) Inability to comprehend or unwillingness to sign the informed consent form (ICF).
21) Unable or unwilling to swallow INCB054828, or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion.
22) Any condition that would in the investigator's judgment interfere with full participation in the study, including administration of study medication and attending required study visits, pose a significant risk to the subject, or interfere with interpretation of study data.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
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