Phase I Dose Escalation and Pharmacokinetics Clinical Trial of Mitoxantrone Hydrochloride Liposome in Children With Relapsed and Refractory Lymphoma and Solid Tumors

Inclusion Criteria:

• 1. Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF);
• 2. 2-21 years old;
• 3. Expected survival ≥ 3 months;

• 4. Subjects with histologically confirmed diagnosis of relapsed and refractory lymphoma and solid tumors, which is one of the following subtypes:

  1. Lymphoblastic lymphoma
  2. Anaplastic large T cell lymphoma
  3. Burkitt's lymphoma
  4. Diffuse large B-cell lymphoma
  5. Peripheral T, NK/T cell lymphoma
  6. Soft tissue sarcoma
  7. Neuroblastoma
  8. Other subtypes of lymphoma or solid tumors that the investigators believe can be included
• 5. Relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (CR) after initial chemotherapy; Refractory lymphoma subjects meet one of the following conditions: 1) The tumor shrinks <50% or disease progression after 4 cycles of standard chemotherapy,; 2) CR after standard chemotherapy, but relapse within half a year; 3) 2 or more relapses after CR; 4) relapse after hematopoietic stem cell transplantation;
• 6. Lymphoma subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length should be > 1.5cm; For non-lymph node lesions, the length should be > 1.0cm;
• 7. Solid tumors must have tumor lesions measurable by CT or MRI;
• 8. ECOG Performance Status: 0-2;
• 9. Bone marrow function: Absolute neutrophil count ≥1.5×109/L, Platelet count ≥75×109/L, Hemoglobin ≥ 80g/L (Absolute neutrophil can be relaxed to ≥ 1.0×109/L, Platelet count can be relaxed to ≥50×109/L, Hemoglobin can be relaxed to ≥75 g/L in subjects with poor bone-marrow reserve);
• 10. Liver and kidney function: serum creatinine ≤ 1.5×ULN (upper limit of normal); AST and ALT ≤ 2.5×ULN (≤ 5×ULN for subjects with liver metastases); total bilirubin ≤ 1.5×ULN (≤ 3×ULN for subjects with liver metastases).

Exclusion Criteria:

• 1. The subject had previously received any of the following anti-tumor treatments:

  1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
  2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin);
  3. Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs;
  4. Subjects who received autologous hematopoietic stem cell transplantation within 100 days after the first medication or allogeneic hematopoietic stem cell transplantation.
• 2. Hypersensitivity to any study drug or its components;
• 3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.);

• 4. Heart function and disease meet one of the following conditions:

  1. Long QTc syndrome or QTc interval > 480 ms;
  2. Complete left bundle branch block, grade II or III atrioventricular block;
  3. Serious and uncontrolled arrhythmias requiring drug treatment;
  4. New York Heart Association grade ≥ III;
  5. Cardiac ejection fraction (LVEF)< 50%;
  6. A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
• 5. Hepatitis B and hepatitis C active infection (plus HBV DNA if one positive for hepatitis B surface antigen or core antibody and HBV DNA more than 1×103 copy/mL excluded; plus HCV RNA if hepatitis C antibody positive and HCV RNA more than 1×103 copy/mL exclude);
• 6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);
• 7. Subjects with other malignant tumors past or present (except for non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in control, and other malignant tumors that have been effectively controlled without treatment within the past five years);
• 8. Subjects suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;
• 9. Pregnant and lactating women and childbearing age patients unwilling to take contraceptive measures;
• 10. Unsuitable subjects for this study determined by the investigator.