Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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T-Cell Neoplasm, Lymphoproliferative Disorders

Intervention / Treatment
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* Drug: Pacritinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pacritinib