Clinical trial NCT04858256: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: T-Cell Neoplasm
Lymphoproliferative Disorders
Keywords: pacritinib
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2021-04-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each of the four disease-based cohorts will be run in parallel, independently, and under an identical two-stage design.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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
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. 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 6 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. Concurrent administration of QTc prolonging agents. Significant QTc prolonging agents must be stopped within 5 half-lives of Cycle 1 Day 1 (see Appendix IV).
14. Uncontrolled diarrhea. NOTE: patients with chronic diarrhea that is well controlled with supportive care measure (e.g. anti-motility agents) are eligible
15. Any gastrointestinal or metabolic condition that in the opinion of the investigator could interfere with the absorption of an oral medication.
16. Prior allogeneic stem-cell transplant.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Complete response rate (CRR)
timeFrame: Up to approximately 5 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 5 years
measure: Time to next treatment (TTNT)
timeFrame: Up to approximately 5 years
measure: Progression- free survival (PFS).
timeFrame: Up to approximately 5 years
measure: Treatment related toxicities >=grade 3
timeFrame: 30 days post end of treatment (+4 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Ryan Wilcox, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: