Clinical Trials /

Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

NCT03601819

Description:

This trial will determine the safety and tolerability of Pacritinib in patients with relapsed/refractory lymphoproliferative disorders.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Peripheral T-Cell Lymphoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders
  • Official Title: Phase Ib, Open Label, Single Center Study of Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.048
  • SECONDARY ID: HUM00144759
  • NCT ID: NCT03601819

Conditions

  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Chronic Lymphocytic Leukemia
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
PacritinibPacritinib

Purpose

This trial will determine the safety and tolerability of Pacritinib in patients with relapsed/refractory lymphoproliferative disorders.

Trial Arms

NameTypeDescriptionInterventions
PacritinibExperimental200 mg twice daily
  • Pacritinib

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of any of the following: Relapsed/refractory cutaneous (stage IIb-IV) or
             peripheral T-cell lymphoma with progression after at least one prior therapy
             (including brentuximab vedotin for patients with anaplastic large cell lymphomas);
             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; any lymphoproliferative disorder who have failed at least 2
             prior therapies 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of dose limiting toxicities (DLT)
Time Frame:Up to 2 years
Safety Issue:
Description:Dose limiting toxicity (DLT) rate on pacritinib 200mg BID with possible dose reductions.

Secondary Outcome Measures

Measure:The proportion of patients that respond to treatment
Time Frame:Up to 2 years
Safety Issue:
Description:Overall response rate (ORR), defined as best disease response recorded from first day of treatment until disease progression or initiation of new antineoplastic therapy. Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.
Measure:The proportion of patients that experience a complete response (CR)
Time Frame:Up to 2 years
Safety Issue:
Description:Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.
Measure:Duration of response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:DOR, defined as time from documented remission to the time of death, relapse, or initiation of alternative antineoplastic. Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.
Measure:Time to next treatment
Time Frame:Up to 2 years
Safety Issue:
Description:Time to next treatment, defined as time from first dose of pacritinib to initiation of alternative antineoplastic therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Trial Keywords

  • Relapsed
  • Refractory
  • MyD88
  • JAK2
  • JAK3
  • TYK2
  • IRAK1
  • CLL
  • SMZL
  • LPL
  • WM
  • MCL
  • CTCL
  • PTCL

Last Updated

June 7, 2019