Golidocitinib With Azacitidine and Chidamide in Patients With Peripheral T-cell Lymphoma.

Official title

An Open-label, Single-arm Study Evaluating the Safety and Efficacy of Golidocitinib Combined With Azacitidine and Chidamide in Patients With Peripheral T-cell Lymphoma.

Overview

In decades, the outcome of patients with peripherial T-cell lymphomas is dismal, especially in relapsed or refractory population. After failure to the frontline treatment, patients have limited treatment options and elderly population usually have no chance to undergo transplantation due to age or comorbidity, etc. Golidocitinib and chidamide were approved in treating r/r PTCL in China, while azacytidine has been demonstrated its anti-tumor activity in PTCL as well. This study aims to explore the efficacy and safety of golidocitinib combined with azacytidine and chidamide in the patients with peripheral T-cell lymphoma who are eligible for intensive chemotherapy or transplantation.

Interventions

• Drug golidocitinib with azacytidine and chidamide
  In Phase I, a "3+3" dose-escalation design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of golidocitinib: 150 mg every other day (QOD) and 150 mg once daily (QD). In Phase II, we aim to evaluate the efficacy and safety of golidocitinib RP2D po in combination with chidamide 20mg biw po and azacytidine 100mg d1-7, SC in patients with peripheral T-cell lymphoma

Primary outcome measures

• Overall Response Rate [Time frame: Tumor evaluation was assessed at screening and at the end of treatment (around 3 cycles) then every 12-24 weeks until disease progression (each cycle is 21 days) through study completion, an average of 1 year]

Secondary outcome measures (5)

• Progression-free survival [Time frame: Baseline up to data cut-off(up to approximately 3 years)]
• Complete Response Rate [Time frame: Tumor evaluation was assessed at screening and at the end of treatment (around 3 cycles) then every 12-24 weeks until disease progression (each cycle is 21 days) through study completion, an average of 1 year.]
• Duration of Response [Time frame: Baseline up to data cut-off(up to approximately 3 years)]
• Overall survival [Time frame: Baseline up to data cut-off(up to approximately 3 years)]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [Time frame: From enrollment to study completion, a maximum of 4 years]

Eligibility criteria

Inclusion criteria

• Histopathologically confirmed peripheral T-cell lymphoma;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2;
• Expected survival of ≥12 weeks;
• Measurable disease lesions;
• Any conditions considered ineligible for intenvive chemotherapy, including but not limted to age > 60 years, at least one comorbidity scored 3 points, or more than 4 comorbidities scored 2 points each according to the CIRS scale;
• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to and adhere to effective contraceptive measures during the treatment period and for 180 days after the last dose of the study drug;
• Participants must voluntarily join the study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up assessments.

Exclusion criteria

• Involvement of the central nervous system (CNS);
• History of malignancies except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix;
• Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
• Left ventricular ejection fraction<50%
• Laboratory measures meet the following criteria at screening (unless caused by lymphoma):

• Neutrophils<1.5×10\^9/L
• Platelets<75×10\^9/L (Platelets<50×10\^9/L in case of bone marrow involvement)
• ALT or AST is 2 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN.
• Creatinine is 1.5 times higher than the ULN.
• HIV-infected patients
• Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
• Pregnant or lactation
• Require treatment with strong/moderate CYP3A inhibitors or inducers.
• Inability to swallow capsules or presence of diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, post-bariatric surgery, inflammatory bowel disease and complete or incomplete intestinal obstruction
• Other medical conditions determined by the researchers that may affect the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07081607 · PTCL-chemofree

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗