Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

NCT03601819 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: UMCC 2018.048HUM00144759
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicities (DLT)

  Dose limiting toxicity (DLT) rate during the 1st cycle (28 days) of pacritinib.

  At 28 days

Secondary Outcomes (4)

• The proportion of patients that respond to treatment

  Up to 2 years

• The proportion of patients that experience a complete response (CR)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Time to next treatment

  Up to 2 years

Study Arms (1)

Pacritinib

EXPERIMENTAL

200 mg twice daily (with possible dose reduction to 100 mg twice daily)

Drug: Pacritinib

Interventions

Pacritinib DRUG

Patients will receive continuous treatment until progressive disease, toxicity, or until any other condition for treatment discontinuation has been met.

Pacritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of any of the following:
• 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
• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoproliferative Disorders; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Recurrence

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma, B-Cell

Study Officials

• Ryan Wilcox, MD, PhD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 26, 2018
• Study Start: May 15, 2019
• Primary Completion: March 7, 2020
• Study Completion: July 17, 2020
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)