A Phase I/II Study of Golidocitinib Combined with Pomalidomide in R/R PTCL

A Phase I/II, Open-Label Clinical Trial to Evaluate the Efficacy and Safety of Golidocitinib As Monotherapy or in Combination with Pomalidomide for the Treatment of Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL)

This is a phase I/II clinical trial to evaluate the efficacy and safety of Golidocitinib combined with Pomalidomide for relapsed/refractory peripheral T-cell lymphoma.

This clinical trial aims to investigate the efficacy and safety of Golidocitinib combined with Pomalidomide in treating relapsed/refractory peripheral T-cell lymphoma (R/R PTCL). The study is a prospective, open-label, phase I/II clinical trial initiated by investigators. It plans to enroll approximately 26-33 patients who have not previously received Golidocitinib or Pomalidomide. The primary endpoint for phase I is to assess the dose-limiting toxicity (DLT) of Pomalidomide in combination with Golidocitinib, estimate the maximum tolerated dose (MTD), and determine the recommended phase II dose (RP2D). For phase II, the primary endpoint is to evaluate the objective response rate (ORR) of the combination therapy. Secondary endpoints include duration of response (DOR), complete response rate (CR), progression-free survival (PFS), overall survival (OS), time to response (TTR), and safety indicators. The study will provide valuable data on the potential benefits and risks of this novel combination therapy for R/R PTCL patients.

Inclusion Criteria:

• Patients must demonstrate a comprehensive understanding of the study protocol, voluntarily consent to participation, and execute the informed consent document.
• Inclusive of both genders, participants must be aged 18 years or older and not exceed 80 years of age.
• Histopathological confirmation of peripheral T-cell lymphoma (PTCL) must adhere to the World Health Organization (WHO) 2016 classification criteria. This encompasses a range of PTCL subtypes, including but not limited to peripheral T cell lymphoma not otherwise specified (PTCL NOS), vascular immunoblastic T cell lymphoma (AITL), NK/T cell lymphoma, anaplastic large cell lymphoma ALK positive (ALCL ALK+), anaplastic large cell lymphoma ALK negative (ALCL ALK-), enteropathy-associated T-cell lymphoma, hepato-splenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and other subtypes deemed eligible for study participation by the investigators.
• Subjects must exhibit relapsed or refractory disease following prior systemic therapy, which may include autologous hematopoietic stem cell transplantation. Relapse is characterized by disease recurrence post-complete response (CR), whereas refractory disease is indicated by stable disease (SD) or progressive disease (PD) following systemic chemotherapy, or by the absence of CR upon treatment completion necessitating further intervention.
• At least one lesion must be present that is evaluable or measurable according to the Lugano2014 criteria: for lymph node lesions, the minimum measurable length is 1.5cm; for non-lymph node lesions, extra-nodal lesions must exceed 1.0cm in length.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score ranging from 0 to 2.
• Laboratory parameters must meet the following criteria: (1) absolute neutrophil count (ANC) of at least 1.5×10^9/L; (2) platelet count (PLT) of at least 75×10^9/L (with a minimum of 50×10^9/L for patients with bone marrow infiltration); (3) hemoglobin (HB) level of at least 80 g/L; (4) serum total bilirubin (TBIL) not exceeding 1.5 times the upper limit of normal (ULN); (5) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels not exceeding 2.5 times the ULN; (6) serum creatinine (Scr) not exceeding 1.5 times the ULN.
• Participants must not have undergone radiotherapy, chemotherapy, targeted therapy, or hematopoietic stem cell transplantation within the 3 weeks preceding study enrollment.
• Investigators must assess that the subject has a life expectancy of at least six months.

Exclusion Criteria:

• Presence of hemophagocytic syndrome.
• Involvement of the central nervous system or meninges by lymphoma.
• A history of malignant tumors within the past five years, with the exception of locally curable tumors that have been subjected to radical treatment (e.g., basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast).
• History of any of the following treatments:(1) Allogeneic hematopoietic stem cell transplantation prior to the administration of the investigational drug; (2) Autologous hematopoietic stem cell transplantation within six months preceding study drug administration; (3) Previous use of golidocitinib or pomalidomide; (4) Current use of vitamin K antagonists, antiplatelet drugs, anticoagulants (or unable to discontinue within one week prior to study commencement); (5) Requirement for systemic glucocorticoid therapy or other immunosuppressive therapy for any condition within 14 days prior to study initiation; topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids are permitted; short-term (≤7 days) glucocorticoid use for prophylactic treatment or non-autoimmune diseases is allowed; (6) Cytotoxic chemotherapy must not have been terminated within 21 days before the start of the study; (7) Received systemic antineoplastic therapy (including macromolecular monoclonal antibodies and immunotherapy drugs) within four weeks of study initiation; (8) Undergone major surgery (excluding vascular access surgery) or experienced serious trauma within four weeks before the start of the study; or received radiation therapy within three weeks; (9) Received other toxin/isotope-immune antibody conjugates within ten weeks; (10) For other types of new drug use, the researcher shall make a determination after comprehensive assessment; (11) Received an experimental drug or investigational drug in another trial within 30 days prior to study commencement; (12) Received live vaccines (except attenuated influenza vaccines) 28 days prior to study drug administration.
• Active infections, including: (1) Known active/latent tuberculosis, including a positive tuberculin skin test or findings on plain chest X-ray/CT (positive skin test results should exhibit an induration diameter greater than 10 mm, or as per local clinical criteria); (2) Known history of Human Immunodeficiency Virus (HIV) infection and/or acquired immunodeficiency syndrome; (3) Patients with active chronic hepatitis B or hepatitis C. Hepatitis B Surface Antigen (HBsAg) must be further tested with Hepatitis B Virus (HBV) DNA titer (not to exceed 1000 IU/mL) at the screening stage. Enrollment in the trial is only possible after excluding active hepatitis B or C infections requiring treatment. Hepatitis B carriers, patients with stable hepatitis B after drug treatment (with a DNA titer not exceeding 1000 IU/mL), and cured hepatitis C patients are eligible for enrollment. (For included hepatitis B patients, entecavir and other anti-hepatitis B virus treatments should be administered orally as per guidelines); (4) Active viral infections other than hepatitis B and C (e.g., herpes zoster, cytomegalovirus); (5) Infections necessitating oral or intravenous antimicrobial therapy; (6) Bacterial infections within 30 days, including pneumonia.
• Active autoimmune diseases requiring systemic treatment within the past two years (hormone replacement therapy not considered systemic treatment, such as type I diabetes, hypothyroidism managed with thyroxine replacement alone, adrenal or pituitary insufficiency requiring only physiological glucocorticoid replacement); patients with autoimmune diseases not requiring systemic treatment in the past two years may be enrolled.
• Uncontrolled cardiac clinical symptoms or diseases, such as: i. New York Heart Association (NYHA) class > 2 heart failure ii. Unstable angina pectoris iii. Myocardial infarction within one year iv. Patients with clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• Prior interstitial lung disease (except for asymptomatic interstitial lung disease induced by radiotherapy).
• Presence of unresolved adverse drug reactions greater than CTCAE grade 1 (excluding alopecia) before study initiation.
• Patients with hypersensitivity to golidocitinib or pomalidomide/capsule excipients or other chemical analogs; patients with a known history of severe allergic reactions to monoclonal antibodies (CTCAE≥3) and uncontrolled allergic asthma.
• Subjects requiring supportive treatment for refractory nausea, vomiting, chronic gastrointestinal disorders, dysphagia, or prior surgical removal of intestinal segments that may impede adequate drug absorption.
• Pregnant and lactating women and individuals of childbearing age who are unwilling to practice contraceptive measures.
• Individuals with psychiatric illnesses or those incapable of providing informed consent.
• Deemed ineligible for study participation by the researcher.