Cutaneous T Cell Lymphoma, Cutaneous T Cell Lymphoma (CTCL), Indolent T-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract, Large Granular Lymphocyte Leukemia, Large Granular Lymphocytic Leukemia, Lymphoma, T-Cell, Mycosis Fungoides, NK-LGL Leukemia, Primary Cutaneous Acral CD8-Positive T-Cell Lymphoma, T-LGL Leukemia
Conditions
Keywords
Indolent T/NK-cell lymphomas, JAK1 inhibitor
Brief summary
Indolent T/NK-cell lymphomas are a heterogeneous group of lymphoproliferative diseases originating from T/NK cells, characterized by slow growth and proliferation, but currently remain incurable. For indolent T/NK-cell lymphomas that are unresponsive to first-line treatment, there are few treatment options available and the prognosis is poor. This study is an open-label, prospective clinical trial aimed at evaluating the feasibility, efficacy, and safety of PI3K inhibitors in the treatment of relapsed/refractory indolent T/NK-cell lymphomas. Patients will be treated with Golidocitnib, with an expected overall response rate of 60% for JAK1 inhibitor Golidocitnib treatment.
Detailed description
Plan to enroll 48 patients with relapsed/refractory indolent T/NK-cell lymphomas; they will receive JAK1 inhibitor treatment (Golidocitnib150mg QD orally, with a 28-day cycle). Efficacy will be evaluated once per cycle during the first year, and once every two cycles thereafter. Treatment will continue for up to 24 cycles, or until disease progression, lack of response within the first 6 cycles, or the occurrence of intolerable toxicity, whichever occurs first.
Interventions
DRUGJAK1 Inhibitor
Golidocitnib 150mg QD orally, with a 28-day cycle. Efficacy will be evaluated once per cycle during the first year, and once every two cycles thereafter. Treatment will continue for up to 24 cycles, or until disease progression, lack of response within the first 6 cycles, or the occurrence of intolerable toxicity, whichever occurs first
Sponsors
Tianjin First Central Hospital
The First Affiliated Hospital of Air Force Medicial University
The First Hospital of Jilin University
The First Affiliated Hospital of Nanchang University
Henan Cancer Hospital
Second Xiangya Hospital of Central South University
Tongji Hospital
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years, with no restrictions on gender; 2. Histologically confirmed relapsed/refractory (R/R) indolent T/NK-cell; lymphoma that has failed at least one systemic therapy or is intolerant to such treatment and/or currently has no effective standard treatment options; 3. The patient meets the criteria for appropriate therapeutic indications; 4. ECOG performance status of 0-2; 5. Adequate organ function, defined as: Total bilirubin (TBIL) ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN; Blood urea nitrogen (BUN)/Urea and creatinine (Cr) ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 50%; Fridericia-corrected QT interval (QTcF): \< 450 ms for males, \< 470 ms for females; 6. An expected survival time of at least 3 months; 7. Male and female subjects of childbearing potential must agree to use effective contraception throughout the study period and for 6 months after the last dose of the investigational drug; 8. A washout period of ≥ 4 weeks since receiving any prior antitumor therapies (including radiotherapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy) before participating in this study; 9. The subject has not participated in any other clinical trial within 1 month prior to enrollment; 10. The subject agrees to and signs the informed consent form.
Exclusion criteria
1. Subjects who have previously used any JAK inhibitors; 2. Subjects with clinical conditions such as dysphagia, malabsorption, or other chronic gastrointestinal diseases that may interfere with compliance and/or absorption of the study drug; 3. Subjects with active viral, bacterial, or fungal infections requiring treatment (e.g., pneumonia); 4. Subjects with HBV or HCV infections, defined as HBsAg and/or HBcAb positivity and HBV DNA copy number ≥ the upper limit of normal (ULN), or acute or chronic active hepatitis C (HCV antibody-positive); 5. Subjects with a history of immunodeficiency, including those who are HIV-positive, or those with other acquired or congenital immunodeficiency diseases, a history of organ transplantation, or a history of allogeneic bone marrow or hematopoietic stem cell transplantation; 6. Subjects who have undergone autologous hematopoietic stem cell transplantation within 90 days prior to the first dose of study treatment; 7. Subjects with severe or uncontrolled cardiovascular diseases; 8. Subjects with severe concomitant diseases that pose a significant risk to patient safety or, in the investigator's judgment, may interfere with the completion of the study (e.g., uncontrolled hypertension, diabetes, or thyroid disorders); 9. Pregnant or breastfeeding female subjects, or baseline positive pregnancy test results in women of childbearing potential; 10. Subjects with a history of other malignancies diagnosed or treated within the past 5 years; 11. Any other conditions that, in the investigator's opinion, render the subject unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | up to 5 years | complete remission rate + partial remission rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remession rate | up to 5 years | Hematological PR was defined as an improvement in blood counts ANC \> 0.5 × 109/L; HGB increased by \>1 g/dL; PLT \> 50 × 109/L |
| Duration of remission | up to 5 years | the time from response to progression/death (P/D) |
| Time to response | up to 5 years | from the start of treatment to the first observed partial remission |
| The safety of JAK1 inhibitor | up to 5 years | Incidence of adverse events, serious adverse events and significant adverse event |
| Overall survival | up to 5 years | The time from the start of treatment to the patient's death from any cause |
| Disease control rate | up to 5 years | the proportion of patients whose tumors have not progressed after treatment over a specific period of time. Specifically, DCR includes the percentage of patients who achieve complete response (CR), partial response (PR), and stable disease (SD). |
| Progression-free survival | up to 5 years | the time from treatment initiation until disease progression or death |
Countries
China
Contacts
Primary ContactShuhua Yi, Doctor
Backup ContactLugui Qiu, Doctor
Outcome results
None listed