Pacritinib in Treating Patients with Relapsed or Refractory Lymphoproliferative Disorders

Inclusion Criteria

• Diagnosis of any of the following: * Relapsed/refractory cutaneous (stage IIb-IV by International Society for Cutaneous Lymphomas [ISCL]/ European Organization for Research and Treatment of Cancer [EORTC] staging criteria) or peripheral T-cell lymphoma with progression after at least one prior therapy (including brentuximab vedotin for patients with anaplastic large cell lymphomas) OR * Chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), Waldenstrom’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) or mantle cell lymphoma (MCL) with disease progression on ibrutinib or who discontinue ibrutinib due to toxicity/intolerance OR * Any lymphoproliferative disorder who have failed at least 2 prior therapies and have had mutational analysis or sequencing studies performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory demonstrating a mutation or gene fusion involving MyD88, JAK2, JAK3, TYK2, or IRAK1 that are known or suspected to be “activating” (gain-of-function)
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN) or =< 5 x ULN in the presence of known hepatic involvement
• Total bilirubin =< 1.5 times ULN (exception of Gilbert disease)
• Creatinine creatinine clearance (CrCl) >= 30 mL/min
• Absolute neutrophil count (ANC) > 500 cells/uL
• Platelets >= 50,000 cells/uL
• Q-T interval Bazett-corrected interval =< 0.45 sec
• Ability to take oral medication without crushing, dissolving or chewing tablets
• In the investigator’s opinion, the patient requires treatment
• Ability to understand and the willingness to sign a written informed consent
• In the investigator’s opinion, the patient has the ability to communicate satisfactorily with the investigator and the study team, to participate fully in the study, and comply with all requirements
• A lymph node biopsy (core-needle or excisional) or skin biopsy is required at enrollment for patients without sufficient archived tissue obtained within 90 days of enrollment

Exclusion Criteria

• 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
• Pregnant or breast feeding women
• 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 for the duration of pacritinib treatment and for 12 months after discontinuation of pacritinib. Fertile males should use contraception for the duration of pacritinib treatment and for 90 days after discontinuation of pacritinib
• Uncontrolled current illness, including, but not limited to the following: * Ongoing or active infections requiring intravenous antimicrobials * Symptomatic congestive heart failure defined as New York Heart Association (NYHA) class II, III, or IV * Unstable angina pectoris within 6 months of study enrollment * Unstable cardiac arrhythmia * History of myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to enrollment * Moderate to severe hepatic impairment (Child-Pugh class B or C). * Psychiatric illness or social situations that would limit compliance with study requirements
• Known human immunodeficiency virus (HIV) infection
• Known positive hepatitis B surface antigen or hepatitis C virus
• Recent (within 21 days of initiation of therapy) major surgery
• Less than 14 days have elapsed since last radiation therapy or chemotherapy treatment and the initiation of therapy (day 1) or patient has not recovered from clinically significant (> grade 2) 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
• Use of systemic steroids (oral, inhaled, nasal, topical) at a dose > 10 mg/day of prednisone
• Prior treatment with pacritinib
• Uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP). Coombs positivity in absence of hemolysis is not an exclusion
• Requires anticoagulation with heparin, warfarin or equivalent vitamin (Vit) K antagonist
• History of significant bleeding history (>= grade 2 by Common Terminology Criteria for Adverse Events[ CTCAE]) or complications (including bleeding that may have occurred while on ibrutinib)
• Hypersensitivity or allergic reaction to compounds related to pacritinib
• Treatment with strong CYP450 inducers or strong CYP3A4 inhibitors, for which no alternative is available. Treatment with strong CYP450 inducers or strong CYP3A4 inhibitors within 2 weeks of initiation of therapy, day 1
• Concurrent administration of corrected QT (QTc) prolonging agents. Significant QTc prolonging agents must be stopped within 5 half-lives of day 1
• Any gastrointestinal or metabolic condition that could interfere with the absorption of oral medication