Golidocitinib for Peripheral T-Cell Lymphoma

Overseen By Luis Malpica Castillo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, JAK inhibitors, others

Disqualifiers: CNS lymphoma, Severe lung disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take medications or supplements that affect CYP3A activity at least one week before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Golidocitinib for treating peripheral T-cell lymphoma?

Golidocitinib, a drug that targets a specific protein involved in cell growth, has shown promising results in early studies for patients with peripheral T-cell lymphoma who did not respond to previous treatments. In a phase 2 study, it demonstrated anti-tumor activity, suggesting it may be effective for this condition. ^{1 2 3 4 5}

Is Golidocitinib safe for humans?

Golidocitinib has been studied in patients with relapsed or refractory peripheral T-cell lymphoma, showing encouraging results in early trials. While specific safety data is not detailed in the provided studies, it has been evaluated in phase 1 and 2 trials, which typically assess safety and tolerability in humans. ^{1 2 6 7 8}

How is the drug Golidocitinib different from other treatments for peripheral T-cell lymphoma?

Golidocitinib is unique because it is an oral drug that specifically targets JAK1, a protein involved in the growth of cancer cells, making it different from traditional chemotherapy which is less targeted. This selectivity may offer a new option for patients with relapsed or refractory peripheral T-cell lymphoma, a condition with limited effective treatments. ^{1 2 8 9 10}

What is the purpose of this trial?

To learn if the study drug golidocitinib given alone or in combination with the standard drug combination therapy called CHOP can help to control PTCL.

Research Team

Luis Malpica Castillo, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals newly diagnosed with Peripheral T Cell Lymphoma (PTCL). Specific eligibility details are not provided, but typically participants must meet certain health standards and may need to have a particular stage or type of PTCL.

Inclusion Criteria

Predicted life expectancy ≥ 12 weeks

Participants must have measurable disease according to the 2014 Lugano classification

Provision of a signed and dated, written informed consent form prior to any study specific procedures, sampling, and analyses

Exclusion Criteria

My heart health meets the study's requirements.

I do not have any severe illnesses, uncontrolled high blood pressure, or active bleeding disorders.

Intervention with investigational anti-cancer agents or anti-cancer study drugs, cytotoxic chemotherapy, corticosteroids at dosages equivalent to prednisone > 40 mg/day within 7 days of the start of the study treatment, major surgery procedure, prior treatment with a JAK or STAT3 inhibitor, prior treatment with any onco-immunotherapy in 28 days prior to first dosing of golidocitinib, live vaccines within 28 days prior to first dose, medications or herbal supplements known to be potent inhibitors or inducers of CYP3A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive golidocitinib alone or in combination with CHOP to control PTCL

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Golidocitinib

Trial Overview The study is testing the effectiveness and safety of golidocitinib, alone or combined with CHOP therapy (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), in treating PTCL. It's a Phase II trial focused on understanding how well this new treatment works.

Participant Groups

Group I: Golidocitinib + CHOP Experimental Treatment 5 Interventions

Golidocitinib will be administered at 150 mg PO daily as monotherapy unless dose modified per toxicity chart; when in combination with CHOP, the maximum dose of golidocitinib is 150 mg PO every other day

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase 2 study involving 104 patients with relapsed or refractory peripheral T-cell lymphoma, golidocitinib demonstrated an objective response rate of 44.3%, indicating significant anti-tumor activity, with 24% of patients achieving a complete response.

While 59% of patients experienced grade 3-4 drug-related adverse events, these were manageable and reversible, suggesting that golidocitinib has a favorable safety profile for further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. Song, Y., Malpica, L., Cai, Q., et al.[2023]

Golidocitinib, a JAK1 selective inhibitor, was found to be safe and tolerable in a phase I/II study involving 51 patients with relapsed or refractory peripheral T-cell lymphomas, with a recommended phase II dose established at 150 mg once daily.

The treatment showed promising antitumor activity, achieving an objective response rate of 39.2% and a complete response rate of 21.6%, indicating its potential effectiveness in a patient population that has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation and expansion study of golidocitinib, a highly selective JAK1 inhibitor, in relapsed or refractory peripheral T-cell lymphomas. Song, Y., Yoon, DH., Yang, H., et al.[2023]

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 phase I/II study involving 28 patients with relapsed/refractory peripheral T-cell lymphomas (PTCLs), the combination of copanlisib and gemcitabine showed a promising overall response rate of 72%, with a complete response (CR) rate of 32%.

The treatment was found to be safe, with manageable adverse events such as transient hyperglycemia and neutropenia, and it demonstrated particularly better outcomes in patients with angioimmunoblastic T-cell lymphoma, highlighting its potential as a new therapeutic option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial. Yhim, HY., Kim, T., Kim, SJ., et al.[2022]

In a study of 108 patients with peripheral T-cell lymphoma (PTCL), a high total metabolic tumor volume (TMTV0) was found to be a strong independent predictor of poor prognosis, with only 26% progression-free survival (PFS) at 2 years for patients with high TMTV0 compared to 71% for those with low TMTV0.

When TMTV0 was combined with the Prognostic Index for T-cell lymphomas (PIT), it further improved the ability to categorize patients into risk groups, showing a stark difference in 2-year PFS (19% for high-risk vs. 73% for low-risk), highlighting its potential as a valuable prognostic marker for PTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL). Cottereau, AS., Becker, S., Broussais, F., et al.[2022]

In a phase 2 trial involving 54 patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), lenalidomide showed a 22% overall response rate, with a notable 31% response rate in patients with angioimmunoblastic T-cell lymphoma (AITL).

While lenalidomide demonstrated efficacy, it also led to significant safety concerns, with 35% of patients experiencing adverse events that required dose adjustments, and serious adverse events occurring in 54% of patients, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Morschhauser, F., Fitoussi, O., Haioun, C., et al.[2020]

Recent advancements have led to the FDA approval of three new agents for relapsed and refractory peripheral T-cell lymphomas (PTCL), including pralatrexate, romidepsin, and brentuximab vedotin, which have shown durable responses in patients with difficult-to-treat disease.

These novel therapies exhibit low cumulative toxicity, allowing for continuous administration without significantly affecting patients' quality of life, and they may serve as effective salvage options for patients eligible for stem-cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for peripheral T-cell lymphomas. Shustov, A.[2021]

In treating the most common types of peripheral T-cell lymphomas (PTCLs), anthracycline-based induction therapy is used, with brentuximab vedotin recommended for anaplastic large cell lymphoma (ALCL) due to its improved survival outcomes without added toxicity.

For relapsed or refractory PTCL, the focus is on achieving complete remission using FDA-approved agents or clinical trials, with the aim of proceeding to allogeneic transplant for curative intent in suitable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Treatment of Peripheral T-cell Lymphoma. Stuver, R., Epstein-Peterson, ZD., Johnson, WT., et al.[2022]

In a study of 341 newly diagnosed patients with peripheral T-cell lymphoma (PTCL), the overall response rate to chemotherapy was 73%, but the 3-year progression-free survival (PFS) and overall survival (OS) rates were only 32% and 52%, respectively, indicating a need for improved treatment strategies.

The analysis found that early-stage disease and the initial response to treatment were the most significant prognostic factors for survival in PTCL patients, while no survival advantage was seen from stem-cell transplantation in first remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. Abramson, JS., Feldman, T., Kroll-Desrosiers, AR., et al.[2021]

Peripheral T-cell lymphomas (PTCLs) are aggressive and respond poorly to traditional chemotherapy, which has been less effective compared to treatments for aggressive B-cell lymphomas.

Recent clinical trials have led to the FDA approval of novel agents specifically targeting PTCL subtypes, showing improved anti-lymphoma responses and overall survival, particularly in relapsed and refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas. Angelos, MG., Ballard, HJ., Barta, SK.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. [2023]

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

Phase I dose escalation and expansion study of golidocitinib, a highly selective JAK1 inhibitor, in relapsed or refractory peripheral T-cell lymphomas. [2023]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL). [2022]

6. England pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Novel therapies for peripheral T-cell lymphomas. [2021]

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

Current Treatment of Peripheral T-cell Lymphoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas. [2023]