Clinical trial NCT03601819 (phase 1, status: terminated)
Conditions: lymphoma, t-cell, cutaneous, lymphoma, t-cell, peripheral, chronic lymphocytic leukemia, lymphoproliferative disorders, waldenstrom macroglobulinemia, lymphoplasmacytic lymphoma, mantle cell lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C91.11, C91.12, C91.10, D47.Z1, C88.0, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: pacritinib
SMILES: C(CN1CCCC1)OC1=CC=C2C=C1COC\C=C\COCC1=CC(=CC=C1)C1=CC=N\C(N1)=N\2
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of any of the following:

               1. Relapsed/refractory cutaneous (stage IIb-IV by ISCL/EORTC staging criteria) or
                  peripheral T-cell lymphoma with progression after the last line of therapy and
                  refractory to/intolerant of or have a contraindication to all established
                  therapies known to provide clinical benefit (including brentuximab vedotin for
                  patients with anaplastic large cell lymphomas) OR

               2. 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. In addition, patients should be refractory
                  to/intolerant of or have a contraindication to all established therapies known to
                  provide clinical benefit OR

               3. Any lymphoproliferative disorder who have failed at least 2 prior therapies and
                  are refractory to/intolerant of or have a contraindication to all established
                  therapies known to provide clinical benefit and have had mutational analysis or
                  sequencing studies performed in a 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).

          -  Age ≥ 18 at time of enrollment

          -  ECOG ≤ 2 (Eastern Cooperative Oncology Group scoring system used to quantify general
             well-being and activities of daily life; scores range from 0 to 5 where 0 represents
             perfect health and 5 represents death.)

          -  Adequate organ and marrow function as defined in the protocol

          -  Ability to take oral medication without crushing, dissolving or chewing tablets.

          -  In the investigator's opinion, the patient requires immediate 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.

        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

          -  Uncontrolled current illness, including, but not limited to the following: Ongoing or
             active infections requiring intravenous antimicrobials; symptomatic congestive heart
             failure defined as NYHA class II, III or IV (Appendix II); 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 HIV infection

          -  Known positive Hepatitis B surface antigen or Hep C virus

          -  Recent (within 21 days of initiation of therapy, day 1) major surgery

          -  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

          -  Use of systemic steroids (oral, inhaled, nasal, topical) at a dose less > 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 Vit K antagonist

          -  History of significant bleeding (≥Grade 2 by CTCAE) history or complications
             (including bleeding that may have occurred while on ibrutinib)

          -  Hypersensitivity or allergic reaction to compounds related to pacritinib

          -  Treatment with potent CYP450 inducers and 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 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