Clinical trial NCT06716658: JAK1 Inhibitor Golidocitnib for the Treatment of Relapsed/refractory Indolent T/NK-cell Lymphomas
Official title: Exploratory Clinical Study of JAK1 Inhibitor Golidocitnib in the Treatment of Relapsed/Refractory Indolent T/NK-Cell Lymphomas：An Open, Prospective, Exploratory Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lymphoma, T-Cell
NK-LGL Leukemia
T-LGL Leukemia
Cutaneous T Cell Lymphoma
Cutaneous T Cell Lymphoma (CTCL)
Large Granular Lymphocyte Leukemia
Large Granular Lymphocytic Leukemia
Indolent T-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract
Primary Cutaneous Acral CD8-Positive T-Cell Lymphoma
Mycosis Fungoides
Keywords: Indolent T/NK-cell lymphomas
JAK1 inhibitor
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Tianjin First Central Hospital
name: The First Affiliated Hospital of Air Force Medicial University
name: The First Hospital of Jilin University
name: The First Affiliated Hospital of Nanchang University
name: Henan Cancer Hospital
name: Second Xiangya Hospital of Central South University
name: Tongji Hospital
First posted: 2024-12-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate
timeFrame: up to 5 years
Secondary outcomes:
measure: The safety of JAK1 inhibitor
timeFrame: up to 5 years
measure: Complete remession rate
timeFrame: up to 5 years
measure: Duration of remission
timeFrame: up to 5 years
measure: Time to response
timeFrame: up to 5 years
measure: Progression-free survival
timeFrame: up to 5 years
measure: Overall survival
timeFrame: up to 5 years
measure: Disease control rate
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, China
state: Tianjin
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
References: