Description:
The main purpose of this study is to determine the effectiveness of the study drug pacritinib in people with relapsed or refractory lymphoproliferative disorders.
The main purpose of this study is to determine the effectiveness of the study drug pacritinib in people with relapsed or refractory lymphoproliferative disorders.
Not yet recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Pacritinib | Cohort 1: PTCL, NOS |
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).
| Name | Type | Description | Interventions |
|---|---|---|---|
| Cohort 1: PTCL, NOS | Experimental | Patients will receive single agent pacritinib. |
|
| Cohort 2: AITL/TFH PTCL | Experimental | Patients will receive single agent pacritinib. |
|
| Cohort 3: CTCL (MF/SS) | Experimental | Patients will receive single agent pacritinib. |
|
| Cohort 4: Less common PTCL subtypes | Experimental | Patients will receive single agent pacritinib. |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Overall response rate (ORR) |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| 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. |
| Measure: | Complete response rate (CRR) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| 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. |
| Measure: | Duration of response (DOR) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| 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. |
| Measure: | Time to next treatment (TTNT) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| 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. |
| Measure: | Progression- free survival (PFS). |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| 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. |
| Measure: | Treatment related toxicities >=grade 3 |
| Time Frame: | 30 days post end of treatment (+4 days) |
| Safety Issue: | |
| 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | University of Michigan Rogel Cancer Center |
April 27, 2021