Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

Phase 2, Open Label, Multicenter Study of Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

The main purpose of this study is to determine the effectiveness of the study drug pacritinib in people with relapsed or refractory lymphoproliferative disorders.

Study Overview

• Status: Recruiting
• Conditions: Lymphoproliferative Disorders; T-Cell Neoplasm
• Intervention / Treatment: Drug: Pacritinib

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).

14NOV2025- Updates were made to the inclusion and exclusion criteria to align with the pacritinib IB v19 and the funders guidance.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Principal Investigator: Christina Poh, MD
      • Contact: Christina Poh; Phone Number: 626-713-7102; Email: cpoh@coh.org
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
      • Contact: Lubomir Sokol; Phone Number: 813-745-6100; Email: lubomir.sokol@moffitt.org
      • Principal Investigator: Lubomir Sokol
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
      • Contact: Cancer AnswerLine; Phone Number: 800-865-1125; Email: CancerAnswerLine@med.umich.edu
      • Principal Investigator: Ryan Wilcox, MD, PhD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Institute
      • Principal Investigator: Jie Wang
      • Contact: Jie Wang; Phone Number: 919-668-1000; Email: jie.wang416@duke.edu
  • Ohio
    • Columbus, Ohio, United States, 43202
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: John Reneau; Phone Number: 614-685-2330; Email: John.Reneau@osumc.edu
      • Principal Investigator: John Reneau
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Not yet recruiting
      • University of Pittsburgh Medical Center
      • Contact: Natalie Galanina; Phone Number: 412-684-7764; Email: galaninan@upmc.edu
      • Principal Investigator: Natalie Galanina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Selected Inclusion Criteria:

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and the willingness to sign a written 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. Sufficient archival tissue (15 unstained slides obtained within 90 days prior to registration) is required. If available, this tissue should be identified at screening and shipped prior to C2D1.If not available, a lymph node or tissue biopsy (core-needle or excisional) or skin biopsy (for CTCL) is required. The type of tissue obtained is at the discretion of the investigator based on disease. NOTE: If archival tissue is not available and a fresh biopsy is inaccessible or technically challenging (per site investigator discretion) at the site, the subject may be eligible for the study.
7. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is based on known history and local policies.
8. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Testing is based on known history and local policies.
9. Ability to take oral medication without crushing, dissolving or chewing tablets.
10. In the investigator's opinion, the patient requires treatment, has an anticipated life expectancy of at least 3 months, and 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.

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. NOTE: women may not breast feed or store breast milk during treatment and for 3 months after pacritinib discontinuation.
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. Women of childbearing potential must use highly effective methods of birth control from the time of informed consent, for the duration of pacritinib treatment and for 30 days after discontinuation of pacritinib. This timeframe also applies to breast-feeding and egg donation. Fertile males must use contraception from the time of study treatment initiation, for the duration of pacritinib treatment and for 30 days after discontinuation of pacritinib. This timeframe is also applicable to sperm donation. Participants should be informed of the risk of unintended pregnancy due to potential reduced effectiveness of hormonal contraceptives sensitive to CYP3A4 metabolism (i.e. progestin) during treatment with pacritinib.

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. Recent (within 21 days of initiation of therapy, day 1) major surgery
6. 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.
7. Use of systemic steroids at a dose equivalent to >10 mg/day of prednisone
8. Prior treatment with pacritinib
9. Requires use of a medication that increases the risk of bleeding, including anticoagulation or antiplatelet therapy with the exception of aspirin at doses of ≤ 100mg daily.
10. History of significant bleeding (≥ Grade 2 by CTCAE), bleeding diatheses, or bleeding complications within the past 3 months.
11. Hypersensitivity or allergic reaction to compounds related to pacritinib.
12. Treatment with strong CYP3A4 inducers or strong CYP3A4 inhibitors (See Appendix III), for which no alternative is available. Treatment with strong CYP3A4 inducers or strong CYP3A4 inhibitors requires a washout period of 2 weeks prior to initiation of therapy, Cycle 1 Day 1.
13. Uncontrolled diarrhea. NOTE: patients with chronic diarrhea that is well controlled with supportive care measure (e.g. anti-motility agents) are eligible
14. Any gastrointestinal or metabolic condition that in the opinion of the investigator could interfere with the absorption of an oral medication.
15. Prior allogeneic stem-cell transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: PTCL, NOS; Patients will receive single agent pacritinib.	Drug: Pacritinib; Pacritinib will be dosed at 200mg twice daily.
Experimental: Cohort 2: AITL/TFH PTCL; Patients will receive single agent pacritinib.	Drug: Pacritinib; Pacritinib will be dosed at 200mg twice daily.
Experimental: Cohort 3: CTCL (MF/SS); Patients will receive single agent pacritinib.	Drug: Pacritinib; Pacritinib will be dosed at 200mg twice daily.
Experimental: Cohort 4: Less common PTCL subtypes; Patients will receive single agent pacritinib.	Drug: Pacritinib; Pacritinib will be dosed at 200mg twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	30 days post end of treatment (+4 days)

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Cancer Institute (NCI); Hoosier Cancer Research Network; National Institutes of Health (NIH); CTI BioPharma
• Investigators: Principal Investigator: Ryan Wilcox, MD, PhD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: pacritinib
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; 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
• Other Study ID Numbers: UMCC 2020.064; R01CA265929 (U.S. NIH Grant/Contract); HUM00184365 (Other Identifier: University of Michigan); HCRN LYM21-544 (Other Identifier: Hoosier Cancer Research Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No