Peripheral T-cell Lymphoma
Conditions
Brief summary
This is single-arm phase I/II study designed to evaluate the safety and efficacy of golcadotinib in combination with the CHOP regimen for patients with newly diagnosed peripheral T-cell lymphoma (PTCL). The study adopts a two-stage design, consisting of a Phase I and a Phase II parts. In the phase I study, a standard 3+3 design will be used. The primary endpoints of the Phase I study are the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). The primary endpoint of the Phase II study is the complete response rate (CRR) of the golcadotinib combined with CHOP regimen.
Interventions
Phase 1: dose escalation phase. Drug Golidocitinib: 2 dose level of 150 mg qod and 150 mg qd; CHOP regimen: cyclophosphamide (750 mg/m2 intravenously on day 1), epirubicin (70 mg/m2 intravenously on day 1), vindesine (4 mg intravenously on day 1), and prednisone (60 mg/m2 orally on days 1-5) in a 3-week cycle. Phase 2: dose expansion phase. Drug Golidocitinib: RP2D established in the phase I study; CHOP regimen: cyclophosphamide (750 mg/m2 intravenously on day 1), epirubicin (70 mg/m2 intravenously on day 1), vindesine (4 mg intravenously on day 1), and prednisone (60 mg/m2 orally on days 1-5) in a 3-week cycle.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 70 years; * Histopathologically confirmed diagnosis of PTCL of one of the following subtypes: (1) Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); (2) Angioimmunoblastic T-cell lymphoma (AITL); (3) Anaplastic large cell lymphoma (ALCL); or (4) other PTCL subtypes considered eligible by the investigator; * Patients must have at least one measurable lesion according to the Lugano 2014 criteria: For lymph node lesions, the measurable lymph node must have a long diameter \>1.5 cm; for non-lymph node lesions, the measurable extranodal lesion must have a long diameter \>1.0 cm; * ECOG performance status score of 0-3; * Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count (PLT) ≥75×10\^9/L, and hemoglobin (HGB) ≥90 g/L (for patients with bone marrow involvement, ANC can be relaxed to ≥1.0×10\^9/L, PLT to ≥50×10\^9/L, and HGB to ≥75 g/L); * Adequate organ function: alanine aminotransferase (ALT) \<3 times the upper limit of normal (ULN), total serum bilirubin (TBIL) ≤1.5 times ULN, creatinine clearance ≥50 mL/min, and left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography.
Exclusion criteria
* Extranodal NK/T-cell lymphoma; * History of acute myocardial infarction or unstable angina, congestive heart failure, symptomatic arrhythmias, or significant QT interval prolongation (men \>450 ms, women \>470 ms) within the past 6 months; * Uncontrolled active infection; * ANC ≤0.5×10\^9/L, lymphocyte count ≤0.4×10\^9/L, PLT ≤75×10\^9/L, ALT ≥3 times the ULN, or creatinine clearance ≤50 mL/min; * Presence of primary or secondary central nervous system (CNS) lymphoma at the time of enrollment; * Pregnant or breastfeeding women; * Patients who have received any investigational drug or radiotherapy within the past 4 weeks; * Individuals deemed unsuitable for participation by the investigator;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase 2 dose (RP2D) of phase 1 study | 4 weeks since the date of first dose] | Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of golidocitinib |
| complete remission rate (CRR) of the phase 2 study | Responses were evaluated after 3 cycles of induction and 1 month after the completion of study therapy (each cycle is 21 days) | Treatment responses were assessed according to the 2014 Lugano classification criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | From date of enrollment until documented disease progression or death of any reason (up to 3 years) | Progression-free survival was defined as the time from the date of enrollment until the date of the first documented day of disease progression or relapse, or death from any cause, whichever occurred first. |
| Overall survival | From date of enrollment until documented death of any reason (up to 3 years) | Overall survival was defined as the time from the date of enrollment to the date of death from any cause. |
| adverse events | From enrollment till 28 days post the last induction cycle | Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Objective Response Rate (ORR) | Responses were evaluated after 3 cycles of induction and 1 month after the completion of study therapy (each cycle is 21 days) | The ORR was defined as the proportion of patients with CR or PR. |
Countries
China
Contacts
Primary ContactWei Zhang, Dr
Outcome results
None listed