Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

Exclusion Criteria

• •1. History of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study
• •2. Pregnant or breast feeding women. NOTE: women may not breast feed or store breast milk during treatment and for 3 months after pacritinib discontinuation.
• •3. Unwilling or unable to use a medically acceptable form of contraception during the time of participation in the trial (sexual abstinence is permissible) unless documented successful vasectomy, hysterectomy, bilateral oophorectomy or post-menopausal for at least 2 years. Women of childbearing potential must use highly effective methods of birth control from the time of informed consent, for the duration of pacritinib treatment and for 30 days after discontinuation of pacritinib. This timeframe also applies to breast-feeding and egg donation. Fertile males must use contraception from the time of study treatment initiation, for the duration of pacritinib treatment and for 30 days after discontinuation of pacritinib. This timeframe is also applicable to sperm donation. Participants should be informed of the risk of unintended pregnancy due to potential reduced effectiveness of hormonal contraceptives sensitive to CYP3A4 metabolism (i.e. progestin) during treatment with pacritinib.
• •4. Uncontrolled current illness, including, but not limited to the following:
• •1. Ongoing or active infections requiring intravenous antimicrobials
• •2. Symptomatic congestive heart failure (CHF) defined as NYHA class II, III or IV (Appendix II), or ejection fraction \<45% in any patient.
• •3. Unstable angina pectoris within 6 months of study enrollment
• •4. Unstable cardiac arrhythmia
• •5. History of myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to enrollment
• •6. Moderate to severe hepatic impairment (Child-Pugh class B or C).
• •7. Psychiatric illness or social situations that would limit compliance with study requirements.
• •5. Recent (within 21 days of initiation of therapy, day 1) major surgery
• •6. Less than 14 days have elapsed since last radiation therapy or chemotherapy treatment or patient has not recovered from all clinically significant treatment related toxicity; less than 90 days have passed since date of autologous stem cell transplant and patient has not recovered to ≤grade 1 toxicity related to this procedure.
• •7. Use of systemic steroids at a dose equivalent to \>10 mg/day of prednisone
• •8. Prior treatment with pacritinib
• •9. Requires use of a medication that increases the risk of bleeding, including anticoagulation or antiplatelet therapy with the exception of aspirin at doses of ≤ 100mg daily.
• •10. History of significant bleeding (≥ Grade 2 by CTCAE), bleeding diatheses, or bleeding complications within the past 3 months.
• •11. Hypersensitivity or allergic reaction to compounds related to pacritinib.
• •12. Treatment with strong CYP3A4 inducers or strong CYP3A4 inhibitors (See Appendix III), for which no alternative is available. Treatment with strong CYP3A4 inducers or strong CYP3A4 inhibitors requires a washout period of 2 weeks prior to initiation of therapy, Cycle 1 Day 1.
• •13. Uncontrolled diarrhea. NOTE: patients with chronic diarrhea that is well controlled with supportive care measure (e.g. anti-motility agents) are eligible
• •14. Any gastrointestinal or metabolic condition that in the opinion of the investigator could interfere with the absorption of an oral medication.
• •15. Prior allogeneic stem-cell transplant.