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Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

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ClinicalTrials.gov Identifier: NCT03601819
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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

Condition or disease Intervention/treatment Phase
Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Chronic Lymphocytic Leukemia Lymphoproliferative Disorders Waldenstrom Macroglobulinemia Lymphoplasmacytic Lymphoma Mantle Cell Lymphoma Drug: Pacritinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib, Open Label, Single Center Study of Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Experimental: Pacritinib
200 mg twice daily
Drug: Pacritinib
Patients will receive continuous treatment until progressive disease, toxicity, or until any other condition for treatment discontinuation has been met.




Primary Outcome Measures :
  1. Rate of dose limiting toxicities (DLT) [ Time Frame: Up to 2 years ]
    Dose limiting toxicity (DLT) rate on pacritinib 200mg BID with possible dose reductions.


Secondary Outcome Measures :
  1. The proportion of patients that respond to treatment [ Time Frame: Up to 2 years ]

    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.


  2. The proportion of patients that experience a complete response (CR) [ Time Frame: Up to 2 years ]
    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.

  3. Duration of response (DOR) [ Time Frame: Up to 2 years ]

    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.


  4. Time to next treatment [ Time Frame: Up to 2 years ]
    Time to next treatment, defined as time from first dose of pacritinib to initiation of alternative antineoplastic therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03601819


Contacts
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Contact: Ryan Wilcox, MD, PhD 734-615-9799 rywilcox@med.umich.edu

Locations
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United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Ryan Wilcox, MD, PhD    734-615-9799    rywilcox@umich.edu   
Principal Investigator: Ryan Wilcox, MD, PhD         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Ryan Wilcox, MD, PhD University of Michigan Rogel Cancer Center

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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03601819     History of Changes
Other Study ID Numbers: UMCC 2018.048
HUM00144759 ( Other Identifier: University of Michigan )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of Michigan Rogel Cancer Center:
Relapsed
Refractory
MyD88
JAK2
JAK3
TYK2
IRAK1
CLL
SMZL
LPL
WM
MCL
CTCL
PTCL

Additional relevant MeSH terms:
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Lymphoma
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders