Golidocitinib Versus Placebo as Maintenance Therapy in PTCL Patients With Response (CR/PR) After First-Line Chemotherapy

Summary

This is a multicenter, randomized, double-blind, phase III clinical study comprising two arms: a golidocitinib group and a placebo group. The study aimed to evaluate the antitumor efficacy and safety of golidocitinib in patients who had achieved a response after first-line systemic therapy and were ineligible for hematopoietic stem cell transplantation. The investigational intervention consisted of either golidocitinib or matching placebo capsules, administered orally at a planned dose of 150 mg once every other day. Treatment continued until disease progression, initiation of new anti-lymphoma therapy, withdrawal of informed consent, death, or investigator decision to discontinue the study, whichever occurred first. The study treatment period was divided into 28-day cycles starting from the first dose. Efficacy and safety assessments were performed at specified time points within each cycle. The maximum duration of treatment was 2 years. A total of 136 patients were enrolled, with 68 patients assigned to the golidocitinib treatment group and 68 to the placebo control group. Data on demographics and medical history were collected, and assessments including vital signs, physical examination, and PET-CT were conducted.

Eligibility

Inclusion Criteria:

* The subject must sign the informed consent form (ICF) in accordance with the relevant procedures described in the chapter, and be willing and able to comply with the requirements and restrictions listed in the ICF and this study protocol.
* Age \>18 years at the time of signing the ICF.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, with no deterioration within the last 2 weeks.
* Histopathologically confirmed diagnosis of PTCL according to the 2016 revised WHO classification of lymphoid neoplasms (Swerdlow SH et al., 2016). Eligible histological subtypes are limited to: PTCL-NOS (excluding primary cutaneous), ALK-negative ALCL, AITL, and follicular helper T-cell lymphoma or PTCL with TFH phenotype (FTCL or PTCL-TFH).
* Subjects must have achieved a Complete Response (CR) or Partial Response (PR) as assessed by the Lugano 2014 criteria following first-line systemic standard therapy (limited to CHOP, BV-CHP, or CHOP-like regimens), and are either transplant-ineligible (age \>65 years) or transplant-eligible (age ≤65 years) but have provided written refusal for transplantation. The time from the end of initial therapy to the planned first dose in this study must be ≤3 months.
* Adequate bone marrow and organ function, as defined below:

  1. Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (≥1.0 × 10⁹/L in case of bone marrow involvement by lymphoma). Subjects must not have used colony-stimulating factors within 7 days prior to study entry.
  2. Platelet count ≥100 × 10⁹/L (≥75 × 10⁹/L in case of bone marrow involvement by lymphoma). Subjects must not have received transfusion or thrombopoietic agents within 7 days prior to study entry.
  3. Hemoglobin ≥10 g/dL.
  4. Total bilirubin ≤2 × Upper Limit of Normal (ULN).
  5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
  6. Serum creatinine ≤1.5 × ULN, OR calculated or measured creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min, OR a 24-hour urine collection demonstrating a creatinine clearance ≥50 mL/min.
* Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiogram (ECHO).
* Voluntarily participate in the clinical study; fully understand and are informed about this study and sign the ICF; willing and able to follow and complete all trial procedures.

Exclusion Criteria:

* Patients with clinical stage Ann Arbor I disease.
* Any of the following treatment histories:

  1. Received any investigational or antitumor drugs in another clinical trial within 30 days prior to the first study dose.
  2. Has not discontinued cytotoxic chemotherapy agents for at least 21 days prior to the first study dose.
  3. Received systemic corticosteroid therapy at a dose \>10 mg prednisone equivalent per day within 1 week prior to the first study dose.
  4. Underwent major surgery (excluding vascular access procedures) or experienced significant trauma within 4 weeks prior to the first study dose, or has planned surgery during the study.
  5. Received antitumor monoclonal antibody therapy (including brentuximab vedotin) within 4 weeks; radiotherapy within 3 weeks; or other toxin/radioisotope-immunoconjugate therapy within 10 weeks prior to the first study dose.
  6. Prior treatment with a JAK or STAT3 inhibitor.
  7. Received antitumor immunotherapy (e.g., immune checkpoint inhibitors including anti-PD-1, anti-PD-L1, anti-CTLA-4) within 28 days prior to the first study dose.
  8. Received live-attenuated or viral vector vaccines within 28 days prior to the first study dose.
  9. Current use (or inability to discontinue ≥1 week prior to the first dose) of vitamin K antagonists, antiplatelet agents, or anticoagulants.

Current use (or inability to discontinue ≥1 week prior to the first dose) of medications, herbal supplements, or foods known to be potent inducers or inhibitors of CYP3A, or sensitive substrates of BCRP/P-gp with a narrow therapeutic index (see Appendix F for guidance on potentially interacting concomitant medications).

* History of other active malignancies within the past 5 years, except for curatively treated localized cancers such as basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
* Active infection, including:

  1. Known active or latent tuberculosis, evidenced by a positive PPD skin test (\>10 mm induration, or per local clinical criteria) or findings suggestive of active/latent TB on chest X-ray/CT.
  2. Known history of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
  3. Chronic active Hepatitis B or C infection, except:

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  1. Subjects positive for HBsAg or HBcAb are eligible if HBV-DNA is undetectable.
  2. Subjects positive for HCV antibody are eligible if HCV-RNA is undetectable. (The ULN for HBV-DNA and HCV-RNA assays is defined per each center's laboratory standards.) (d) Other active viral infections (e.g., herpes zoster), cytomegalovirus (CMV), or Epstein-Barr virus (EBV) infection, excluding Hepatitis B and C.

Active infection requiring intravenous antimicrobial therapy, characterized by hemodynamic instability, worsening/new infectious symptoms/signs, new infectious foci on imaging, or persistent fever without other explanation.

* Poorly controlled or clinically significant cardiac disease, such as:

  i. Heart failure \> New York Heart Association (NYHA) class II. ii. Unstable angina. iii. Myocardial infarction within the past year. iv. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
* Pregnant or lactating women, or subjects of childbearing potential unwilling to use effective contraception.
* History of severe psychiatric disorders or inability to provide informed consent.
* Subjects with refractory nausea, vomiting, or chronic gastrointestinal diseases that may impair drug absorption.
* Significant impairment of pulmonary function, defined as forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) \<60% of predicted.
* Presence of unresolved drug-related toxicities \> Grade 1 per CTCAE (except for alopecia) prior to the first study dose.
* Any other condition that, in the investigator's judgment, would make the subject unsuitable for participation in this study.

Conditions2

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