This is a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating golidocitinib as maintenance therapy in adult patients with peripheral T-cell lymphoma (PTCL) who achieved complete response (CR) or partial response (PR) after first-line systemic chemotherapy and are not candidates for hematopoietic stem cell transplantation (HSCT) or decline HSCT. Eligible patients with histologically confirmed PTCL subtypes (PTCL-NOS, ALK-positive anaplastic large cell lymphoma \[ALK-ALCL\], angioimmunoblastic T-cell lymphoma \[AITL\], or follicular helper T-cell phenotype PTCL \[FTCL/PTCL-TFH\]) according to the 2016 WHO classification will be randomized 1:1 to receive oral golidocitinib or matching placebo. Study treatment is given at 150 mg every other day in 28-day cycles for up to 2 years or until disease progression, unacceptable toxicity, start of new anti-lymphoma therapy, withdrawal of consent, or study termination. At 12 months, patients who achieve complete metabolic response on PET-CT and minimal residual disease (MRD)-negative status by ctDNA may discontinue maintenance, whereas others continue treatment up to 24 months. After treatment discontinuation, patients will be followed for disease status and survival for up to approximately 13 additional cycles. The primary endpoint is progression-free survival (PFS) assessed by investigators per Lugano 2014 criteria. Key secondary endpoints include overall survival, response rates, duration of response, time to next anti-lymphoma therapy, MRD dynamics by ctDNA, and safety.
Peripheral T-cell lymphomas (PTCL) are aggressive non-Hodgkin lymphomas with poor prognosis and high relapse rates after first-line chemotherapy. There is no established standard of care for post-remission maintenance therapy in patients who are not candidates for hematopoietic stem cell transplantation. Aberrant activation of the JAK/STAT pathway plays a critical role in the pathogenesis and progression of PTCL. Golidocitinib (Chinese name: 戈利昔替尼) is an oral, potent, and highly selective JAK1 inhibitor that has demonstrated robust antitumor activity and a favorable safety profile in relapsed or refractory PTCL in prior clinical studies, leading to its recommended phase II dose of 150 mg once daily. Based on these data and the unmet need for effective maintenance strategies, this phase III study (T-START-M1) will enroll adult patients with histologically confirmed PTCL subtypes (PTCL-NOS excluding primary cutaneous disease, ALK-ALCL, AITL, FTCL/PTCL-TFH) who achieved CR or PR after first-line CHOP, BV-CHP, or CHOP-like regimens and are ineligible for HSCT (age \>65 years) or decline HSCT despite eligibility. Randomization (1:1) will be stratified by initial response status (CR vs PR), histologic subtype (ALK-ALCL vs others), and HSCT eligibility (ineligible vs eligible-but-declining). Participants will receive golidocitinib 150 mg every other day or matching placebo in 28-day cycles for up to 24 months. Tumor response will be assessed by imaging according to Lugano 2014 criteria, and ctDNA-based MRD will be evaluated at baseline, 12 months, and end of treatment. Patients who achieve complete metabolic response plus MRD negativity at 12 months may stop maintenance, while others continue up to 2 years. After treatment discontinuation, patients will be followed for progression, subsequent anti-lymphoma therapies, and survival for up to approximately 13 additional cycles (about 1 year). The primary objective is to determine whether golidocitinib maintenance improves PFS compared with placebo. Key secondary objectives include evaluation of overall survival, complete response rate, duration of response, time to next anti-lymphoma therapy, ctDNA-based MRD dynamics, and safety including incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and grade ≥3 AEs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
136
The patients who achieved CMR by PET-CT and MRD-neg by ct-DNA testing were evaluated at 12 months,One patient stopped maintenance treatment, while the rest continued for one year.
Fudan University Shanghai Cancer Center
Shanghai, China
Progression-free Survival (PFS)
PFS is defined as the time from randomization to the first documented disease progression or relapse according to Lugano 2014 criteria, or death from any cause, whichever occurs first, as assessed by investigators. A blinded independent central review (BICR) will perform a sensitivity analysis of PFS to assess robustness.
Time frame: From randomization to the first documentation of disease progression, relapse, or death from any cause, up to approximately 3 years.
Overall Survival (OS)
Time from randomization to death from any cause.
Time frame: From randomization until death from any cause, up to approximately 5 years.
Complete Response Rate (CRR)
Proportion of patients achieving complete response (CR) according to Lugano 2014 criteria.
Time frame: From randomization to end of treatment, up to 24 months.
Duration of Response (DOR)
Duration of response among patients who achieve CR or PR.
Time frame: From the first documented response (CR or PR) to disease progression, relapse, or death, up to approximately 3 years.
Time to Next Anti-lymphoma Therapy (TTNT)
ime from randomization to the first administration of subsequent anti-lymphoma therapy or death.
Time frame: From randomization to the start of the next systemic anti-lymphoma therapy or death, up to approximately 3 years.
MRD Negativity Rate by ctDNA at 12 Months
Proportion of patients who achieve minimal residual disease (MRD)-negative status by ctDNA assessment at 12 months.
Time frame: 12 months after randomization.
Incidence of Treatment-emergent Adverse Events (TEAEs)
Number and percentage of patients experiencing TEAEs, serious adverse events (SAEs), grade ≥3 AEs, AEs leading to dose interruption, dose reduction, or treatment discontinuation.
Time frame: From first dose of study drug to 28 days after the last dose.
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