A Phase Ib/II Clinical Study of Mitoxantrone Liposome and Azacitidine in the Treatment of Relapsed/Refractory Angioimmunoblastic T-cell Lymphoma
This study is an open-label, single-arm Phase Ib/II clinical trial designed to evaluate the safety and efficacy of the combination therapy with mitoxantrone liposome and azacitidine in the treatment of relapsed/refractory angioimmunoblastic T-cell lymphoma(R/R AITL). The study includes two parts: a dose escalation phase and a dose expansion phase, each comprising screening, treatment, and follow-up periods. In the dose escalation phase, the mitoxantrone liposome injection will start at a dose of 16 mg/m\^2 on day1, combined with subcutaneous injection of azacitidine at a dose of 75 mg/m\^2 on days 1-7, with each cycle lasting 4 weeks (28 days). Three predetermined dose groups for mitoxantrone liposome are 16, 18, and 20 mg/m\^2. In the dose expansion phase, 10-20 cases will be included with the mitoxantrone liposome injection at the recommended phase II dose (RP2D) based on the results of the dose escalation phase. After the treatment period, safety and survival information will be collected during the follow-up period. This study aims to comprehensively evaluate the safety and efficacy of mitoxantrone liposome in combination with azacitidine for the treatment of R/R AITL, exploring a combination therapy that offers higher survival benefits with limited adverse reactions and providing new therapeutic approaches for R/R AITL.
• The patient fully understands this study and voluntarily participates,willingly chooses to participate, and signs the informed consent form (ICF), expressing the willingness to comply with and having the capability to complete all trial procedures;
• Male or female patients aged 18 to 75(including 18 and 70 years old);
• ECOG score 0-2 points;
• Angioimmunoblastic T-cell lymphoma (AITL) confirmed by histopathology;
• Relapsed/refractory patients who have received at least first-line anthracyclines containing systematic therapy in the past. Relapsed lymphoma refers to lymphoma that relapses after obtaining a complete response (CR) or partial response(PR) after initial therapy.Refractory lymphoma is defined as progressive disease in the first chemotherapy cycle 2, or stable disease in the first chemotherapy cycle 4;
• There must be at least one measurable lesion that meets the Lugano2014 standard: a lymph node lesion, with a measurable lymph node length greater than 1.5cm in diameter; Non lymph node lesions, measurable extranodal lesions with a length diameter greater than 1.0cm;
• During patient screening, laboratory tests must meet the following requirements, and the patient should not have received any hematopoietic growth factors, platelet, or granulocyte transfusions within the 7 days prior to the hematological assessment during screening:
‣ neutrophil count ≥ 1.5 x 10\^9/L, it can be relaxed to ≥ 1.0 x 10\^9 /L in patients with bone marrow involvement;
⁃ hemoglobin ≥ 90 g/L(without red blood cell transfusion within 14 days), it can be relaxed to ≥ 75 g/L in patients with bone marrow involvement;
⁃ platelet count ≥ 75 x 10\^9 /L, it can be relaxed to ≥ 50 x 10\^9 /L in patients with bone marrow involvement;
⁃ Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver invasion);
⁃ AST and ALT ≤ 2.5 times the upper limit of normal values ,≤ 5 times the upper limit of normal values for patients with liver invasion;
⁃ Serum creatinine ≤ 1.5 times the upper limit of normal value; 8.Qualified patients of reproductive capability (both males and females) must agree to use a reliable contraceptive method with their partners during the trial and for at least 7 months after the last dose of medication. Female patients of childbearing age must have a negative blood pregnancy test within 7 days prior to enrollment.