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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug golidocitinib, either alone or with standard CHOP therapy, can effectively control peripheral T-cell lymphoma (PTCL), a type of blood cancer. It will test golidocitinib both by itself and in combination with CHOP to identify the best treatment approach for PTCL. Individuals diagnosed with PTCL who have not yet received any treatment may be eligible to participate. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that golidocitinib is likely to be safe for humans?

Studies have shown that golidocitinib, a treatment for peripheral T-cell lymphoma (PTCL), generally maintains a good safety record. One study found that golidocitinib offers a favorable balance of benefits and risks for patients whose PTCL has returned or not responded to other treatments. However, 59% of patients experienced serious side effects related to the drug. These side effects often involved changes in blood cell counts, such as a decrease in white blood cells, which can increase the risk of infections.

While researchers continue to test golidocitinib, current research enhances understanding of its safety in people. Prospective clinical trial participants can use this information to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Golidocitinib is unique because it targets a specific enzyme known as JAK1, which plays a crucial role in the growth of cancer cells in peripheral T-cell lymphoma. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Golidocitinib offers a more targeted approach, potentially leading to fewer side effects. Additionally, its ability to be administered orally as a pill makes it more convenient than many existing treatments that require intravenous administration. Researchers are excited about Golidocitinib because it offers a novel mechanism of action that could improve outcomes for patients with this type of lymphoma.

What evidence suggests that golidocitinib could be an effective treatment for PTCL?

Research has shown that golidocitinib, a drug targeting the JAK1 protein, may help treat peripheral T-cell lymphoma (PTCL). In one study, 44% of patients with PTCL that had returned or didn't respond to other treatments experienced significant improvement after taking golidocitinib. This trial will evaluate golidocitinib in combination with CHOP chemotherapy. Findings from previous studies suggest that golidocitinib can effectively manage the disease for many patients. Additionally, the drug has demonstrated a good balance between benefits and risks, indicating that for many patients, the advantages outweigh the potential downsides. These findings suggest that golidocitinib could be a promising treatment option for PTCL. ^{1 2 3 4 5}

Who Is on the Research Team?

Luis Malpica Castillo, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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 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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00828-1/fulltext

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

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6368/528066/Maintenance-Therapy-of-Golidocitinib-a-JAK1

Maintenance Therapy of Golidocitinib, a JAK1 Selective ... Approximately 40% of patients with complete response and 80% of patients with partial response had disease relapse within 2 years after initial tumor response, ...

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35272

Golidocitinib favorable for relapsed/refractory T‐cell lymphoma Among 88 heavily pretreated patients with relapsed/refractory PTCL treated with golidocitinib, 44% achieved an objective response rate (ORR) and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38092009/

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in ... In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06630091

Study Details | NCT06630091 | A Phase II, Single-center, ... To assess the 2-year progression-free survival rate of golidocitinib as primary efficacy endpoint in participants with newly diagnosed PTCL. Secondary ...