Pacritinib for T-Cell Lymphoma

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Systemic steroids, Anticoagulants, Antiplatelets, others

Disqualifiers: Pregnancy, Heart failure, Recent surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Do I need to stop taking my current medications for the trial?

The trial requires a 2-week break from strong CYP3A4 inducers or inhibitors before starting the study drug. Also, medications that prolong QTc must be stopped within 5 half-lives before starting the trial. If you are on these medications, you may need to stop or adjust them.

What makes the drug Pacritinib unique for treating T-cell lymphoma?

Pacritinib is unique because it is a targeted therapy that inhibits specific enzymes involved in cancer cell growth, which may offer a novel approach compared to traditional chemotherapy regimens used for T-cell lymphoma. This could potentially provide an option for patients who do not respond well to existing treatments. ^{1 2 3 4 5}

Research Team

Ryan Wilcox, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

This trial is for adults with certain types of T-cell lymphoma that have not responded to previous treatments or have come back after treatment. Participants must be able to take pills, understand and comply with study procedures, and use effective contraception if necessary. They should not have severe psychiatric issues, gastrointestinal conditions affecting drug absorption, uncontrolled illnesses like heart disease or infections, nor should they be pregnant.

Inclusion Criteria

I can swallow pills without needing to break them down.

Ability to give informed consent

My disease came back or didn't respond to treatment within 6 months.

Exclusion Criteria

I don't have stomach or metabolic issues affecting medicine absorption.

I have not had major surgery in the last 3 weeks.

I have stopped taking medications that affect my heart's rhythm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive single-agent treatment with pacritinib 200mg orally twice daily until any condition for treatment discontinuation has been met

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post end of treatment

Long-term follow-up

Participants are monitored for long-term outcomes such as progression-free survival and duration of response

Up to approximately 5 years

Treatment Details

Interventions

• Pacritinib

Trial Overview The trial is testing the effectiveness of a medication called Pacritinib in patients who have relapsed (cancer has returned) or refractory (not responding to treatment) T-cell lymphoproliferative disorders. The focus is on how well this oral drug works against these specific types of cancer.

Participant Groups

Group I: Cohort 4: Less common PTCL subtypes Experimental Treatment 1 Intervention

Patients will receive single agent pacritinib.

Group II: Cohort 3: CTCL (MF/SS) Experimental Treatment 1 Intervention

Patients will receive single agent pacritinib.

Group III: Cohort 2: AITL/TFH PTCL Experimental Treatment 1 Intervention

Patients will receive single agent pacritinib.

Group IV: Cohort 1: PTCL, NOS Experimental Treatment 1 Intervention

Patients will receive single agent pacritinib.

Pacritinib is already approved in United States for the following indications:

Approved in United States as Vonjo for:

• Intermediate or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10^9/L

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 420 patients with peripheral T-cell lymphoma (PTCL), those with relapsed disease had a significantly higher objective response rate (61%) and complete response rate (41%) to second-line therapy compared to primary refractory patients, who had response rates of 40% and 14%, respectively.

Relapsed patients also experienced better overall survival, with a median of 29.1 months, compared to 12.3 months for refractory patients, highlighting the need for improved front-line therapies for PTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry. Lansigan, F., Horwitz, SM., Pinter-Brown, LC., et al.[2020]

In a study of 1344 patients with peripheral T-cell lymphoma (PTCL), those treated with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A + CHP) had a lower rate of subsequent therapy compared to those treated with CHOP, indicating potentially better initial treatment efficacy.

The study highlighted that patients in the real-world setting were older and had more comorbidities than those in clinical trials, emphasizing the need for retrospective analyses to understand the impact of new treatments in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy. Burke, JM., Liu, N., Yu, KS., et al.[2023]

Alisertib (MLN8237), an oral Aurora A kinase inhibitor, has demonstrated the ability to reduce cell proliferation and induce apoptosis in various tumor cell lines, making it a promising treatment for aggressive peripheral T-cell lymphomas.

Currently undergoing Phase III trials, alisertib has shown single-agent antitumor activity in animal models and potential effectiveness in patients with relapsed or refractory peripheral T-cell lymphoma, highlighting its importance in developing new therapies for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of alisertib in treatment of peripheral T-cell lymphomas. Gallop-Evans, E.[2015]

Peripheral T-cell lymphoma (PTCL) accounts for about 10% of non-Hodgkin lymphoma cases and includes 23 recognized subtypes, with patients often being more resistant to initial therapies compared to aggressive B-cell lymphomas.

For common nodal PTCL subtypes, anthracycline-based regimens followed by high-dose therapy and autologous stem cell transplantation (ASCT) in first chemosensitive remission yield the best outcomes, while several FDA-approved agents are available for relapsed or refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Peripheral T-Cell Lymphoma: Many Shades of Gray. Lunning, MA.[2015]

In a study of 20 patients with relapsed/refractory peripheral T-cell lymphoma, the combination of camrelizumab (a PD-1 inhibitor) and apatinib (an antiangiogenic agent) showed a 30% overall response rate, with 10% of patients achieving a complete response.

The treatment was found to have manageable safety, with common grade 3 or higher adverse events including hyperlipidemia, hypokalemia, and anemia, but no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity and safety of camrelizumab combined with apatinib in patients with relapsed or refractory peripheral T-cell lymphoma: An open-label, multicenter, phase II study. Liu, Y., Song, Y., Zuo, S., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The role of alisertib in treatment of peripheral T-cell lymphomas. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of Peripheral T-Cell Lymphoma: Many Shades of Gray. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Antitumor activity and safety of camrelizumab combined with apatinib in patients with relapsed or refractory peripheral T-cell lymphoma: An open-label, multicenter, phase II study. [2023]