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Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

Primary Purpose

T-Cell Neoplasm, Lymphoproliferative Disorders

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pacritinib
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-Cell Neoplasm focused on measuring pacritinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Selected Inclusion Criteria:

  1. Ability to give informed consent.
  2. ECOG performance status ≤ 2
  3. A histologically confirmed diagnosis, per the WHO 2016 classification, of any PTCL or CTCL subtype listed in the protocol.
  4. Relapsed or refractory disease. Refractory disease is defined as progression during treatment or recurrent/progressive disease within 6 months of completing a treatment regimen that achieved either stable disease or a PR/CR. Relapsed disease is defined as progression or recurrence at least 6 months after a prior documented response (PR or CR).
  5. Adequate organ and hematopoietic function as defined in the protocol.
  6. Ability to take oral medication without crushing, dissolving or chewing tablets.
  7. 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, comply with all requirements, and has an anticipated life expectancy of at least 3 months.

Selected Exclusion Criteria:

  1. 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
  2. Pregnant or breast feeding women
  3. 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.
  4. Uncontrolled current illness, including, but not limited to the following:

    1. Ongoing or active infections requiring intravenous antimicrobials
    2. Symptomatic congestive heart failure (CHF) defined as NYHA class II, III or IV (Appendix II), or ejection fraction <45% in any patient.
    3. Unstable angina pectoris within 6 months of study enrollment
    4. Unstable cardiac arrhythmia
    5. History of myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to enrollment
    6. Moderate to severe hepatic impairment (Child-Pugh class B or C).
    7. Psychiatric illness or social situations that would limit compliance with study requirements.
  5. Known HIV infection
  6. Known Hepatitis B or Hepatitis C infection
  7. Recent (within 21 days of initiation of therapy, day 1) major surgery
  8. Less than 14 days have elapsed since last radiation therapy or chemotherapy treatment or patient has not recovered from all clinically significant treatmentrelated 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.
  9. Use of systemic steroids at a dose equivalent to >10 mg/day of prednisone
  10. Prior treatment with pacritinib
  11. Requires anticoagulation with heparin, warfarin or equivalent Vit K antagonist
  12. History of significant bleeding (≥ Grade 2 by CTCAE), bleeding diatheses, or bleeding complications within the past 6 months.
  13. Treatment with potent CYP450 inducers and strong CYP3A4 inhibitors (See Appendix IV), for which no alternative is available. Treatment with strong CYP450 inducers or strong CYP3A4 inhibitors within 2 weeks of initiation of therapy, day 1.
  14. Concurrent administration of QTc prolonging agents. Significant QTc prolonging agents must be stopped within 5 half-lives of day 1.
  15. Any gastrointestinal or metabolic condition that could interfere with the absorption of oral medication.
  16. Prior allogeneic stem cell transplant.

Sites / Locations

  • City of Hope
  • Moffitt Cancer Center
  • University of Michigan Rogel Cancer CenterRecruiting
  • Duke Cancer Institute
  • Ohio State University Comprehensive Cancer Center
  • University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: PTCL, NOS

Cohort 2: AITL/TFH PTCL

Cohort 3: CTCL (MF/SS)

Cohort 4: Less common PTCL subtypes

Arm Description

Patients will receive single agent pacritinib.

Patients will receive single agent pacritinib.

Patients will receive single agent pacritinib.

Patients will receive single agent pacritinib.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
ORR will be estimated for each disease-specific cohort of patients. Overall response is defined as best disease response recorded from first day of treatment until disease progression or treatment discontinuation. Response in PTCL patients is assessed by PET/CT scan using the Response Evaluation Criteria in Lymphoma (RECIL) criteria. Response in CTCL patients is assessed using the modified Severity Weighted Assessment Tool (mSWAT). Results will be stratified by type: complete response [CR], partial response [PR], minor response [MR; a provisional category in RECIL only], stable disease [SD], progressive disease [PD]; and by cohort.

Secondary Outcome Measures

Complete response rate (CRR)
CRR is defined as the percentage of PTCL patients who have a best response of CR per the RECIL criteria and percentage of CTCL who a have a best response of CR per the modified Severity Weighted Assessment Tool (mSWAT). CR rate will be analyzed by cohort and summarized with "time-to-event" analysis.
Duration of response (DOR)
DOR is defined as time from first observed response (CR or PR) to date of progression (PD) or death, whichever occurs first. DOR will be analyzed by cohort with "time-to-event" analysis.
Time to next treatment (TTNT)
TTNT is defined as time from first dose of pacritinib to initiation of alternative systemic, antineoplastic therapy. TTNT will be analyzed by cohort using a "time-to-event" analysis.
Progression- free survival (PFS).
PFS is defined as the time from first day of treatment to date of disease progression (PD) or death, whichever occurs first. Patients who survive without progression will be censored on the date of last evaluable tumor assessment. PFS will be analyzed by cohort and summarized with "time-to-event analysis.
Treatment related toxicities >=grade 3
The analyses of safety endpoint will be conducted using tabulations of adverse events, assessed per NCI CTCAE v5.0, stratified by grade (severity) and attribution for each cohort. Grade 3 or higher treatment related toxicities will be reported.

Full Information

First Posted
April 20, 2021
Last Updated
July 18, 2023
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04858256
Brief Title
Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms
Official Title
Phase 2, Open Label, Multicenter Study of Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2023 (Actual)
Primary Completion Date
November 2027 (Anticipated)
Study Completion Date
November 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The main purpose of this study is to determine the effectiveness of the study drug pacritinib in people with relapsed or refractory lymphoproliferative disorders.
Detailed Description
Patients will receive single-agent treatment with pacritinib 200mg orally twice daily until any condition for treatment discontinuation has been met. Patients will be enrolled into one of four cohorts: Peripheral T-Cell Lymphoma, not otherwise specified (PTCL, NOS) (cohort 1); angioimmunoblastic T-cell lymphoma/follicular helper T-cell (AITL/TFH) PTCL (cohort 2); Cutaneous T-Cell Lymphoma (CTCL) - mycosis fungoides (MF) and Sezary syndrome (SS) (cohort 3); and other eligible, less common PTCL subtypes (cohort 4).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-Cell Neoplasm, Lymphoproliferative Disorders
Keywords
pacritinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Each of the four disease-based cohorts will be run in parallel, independently, and under an identical two-stage design.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: PTCL, NOS
Arm Type
Experimental
Arm Description
Patients will receive single agent pacritinib.
Arm Title
Cohort 2: AITL/TFH PTCL
Arm Type
Experimental
Arm Description
Patients will receive single agent pacritinib.
Arm Title
Cohort 3: CTCL (MF/SS)
Arm Type
Experimental
Arm Description
Patients will receive single agent pacritinib.
Arm Title
Cohort 4: Less common PTCL subtypes
Arm Type
Experimental
Arm Description
Patients will receive single agent pacritinib.
Intervention Type
Drug
Intervention Name(s)
Pacritinib
Intervention Description
Pacritinib will be dosed at 200mg twice daily.
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR will be estimated for each disease-specific cohort of patients. Overall response is defined as best disease response recorded from first day of treatment until disease progression or treatment discontinuation. Response in PTCL patients is assessed by PET/CT scan using the Response Evaluation Criteria in Lymphoma (RECIL) criteria. Response in CTCL patients is assessed using the modified Severity Weighted Assessment Tool (mSWAT). Results will be stratified by type: complete response [CR], partial response [PR], minor response [MR; a provisional category in RECIL only], stable disease [SD], progressive disease [PD]; and by cohort.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
CRR is defined as the percentage of PTCL patients who have a best response of CR per the RECIL criteria and percentage of CTCL who a have a best response of CR per the modified Severity Weighted Assessment Tool (mSWAT). CR rate will be analyzed by cohort and summarized with "time-to-event" analysis.
Time Frame
Up to approximately 5 years
Title
Duration of response (DOR)
Description
DOR is defined as time from first observed response (CR or PR) to date of progression (PD) or death, whichever occurs first. DOR will be analyzed by cohort with "time-to-event" analysis.
Time Frame
Up to approximately 5 years
Title
Time to next treatment (TTNT)
Description
TTNT is defined as time from first dose of pacritinib to initiation of alternative systemic, antineoplastic therapy. TTNT will be analyzed by cohort using a "time-to-event" analysis.
Time Frame
Up to approximately 5 years
Title
Progression- free survival (PFS).
Description
PFS is defined as the time from first day of treatment to date of disease progression (PD) or death, whichever occurs first. Patients who survive without progression will be censored on the date of last evaluable tumor assessment. PFS will be analyzed by cohort and summarized with "time-to-event analysis.
Time Frame
Up to approximately 5 years
Title
Treatment related toxicities >=grade 3
Description
The analyses of safety endpoint will be conducted using tabulations of adverse events, assessed per NCI CTCAE v5.0, stratified by grade (severity) and attribution for each cohort. Grade 3 or higher treatment related toxicities will be reported.
Time Frame
30 days post end of treatment (+4 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Selected Inclusion Criteria: Ability to give informed consent. ECOG performance status ≤ 2 A histologically confirmed diagnosis, per the WHO 2016 classification, of any PTCL or CTCL subtype listed in the protocol. Relapsed or refractory disease. Refractory disease is defined as progression during treatment or recurrent/progressive disease within 6 months of completing a treatment regimen that achieved either stable disease or a PR/CR. Relapsed disease is defined as progression or recurrence at least 6 months after a prior documented response (PR or CR). Adequate organ and hematopoietic function as defined in the protocol. Ability to take oral medication without crushing, dissolving or chewing tablets. 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, comply with all requirements, and has an anticipated life expectancy of at least 3 months. Selected 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 (CHF) defined as NYHA class II, III or IV (Appendix II), or ejection fraction <45% in any patient. 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 Hepatitis B or Hepatitis C infection 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 treatmentrelated 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 at a dose equivalent to >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), bleeding diatheses, or bleeding complications within the past 6 months. Treatment with potent CYP450 inducers and strong CYP3A4 inhibitors (See Appendix IV), 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. Prior allogeneic stem cell transplant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Wilcox, MD, PhD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jasmine Zain
Phone
626-471-9300
Email
jazain@coh.org
First Name & Middle Initial & Last Name & Degree
Jasmine Zain
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lubomir Sokol
Phone
813-745-6100
Email
lubomir.sokol@moffitt.org
First Name & Middle Initial & Last Name & Degree
Lubomir Sokol
Facility Name
University of Michigan Rogel Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer AnswerLine
Phone
800-865-1125
Email
CancerAnswerLine@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Ryan Wilcox, MD, PhD
Facility Name
Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Wang
Phone
919-668-1000
Email
jie.wang416@duke.edu
First Name & Middle Initial & Last Name & Degree
Jie Wang
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43202
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Reneau
Phone
614-685-2330
Email
John.Reneau@osumc.edu
First Name & Middle Initial & Last Name & Degree
John Reneau
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Galanina
Phone
412-684-7764
Email
galaninan@upmc.edu
First Name & Middle Initial & Last Name & Degree
Natalie Galanina

12. IPD Sharing Statement

Plan to Share IPD
No

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Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

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