Diffuse Large B-cell Lymphoma
Conditions
Brief summary
To evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with rituximab and lenalidomide in the treatment of relapsed and refractory diffuse large B-cell lymphoma (DLBCL).
Detailed description
This is a prospective, single-arm, multicenter phase Ⅱ clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with rituximab and lenalidomide in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). Mitoxantrone hydrochloride liposome will be given on day 1 at the dose of 20 mg/m2 and be combined with rituximab and lenalidomide. A maximum of 6 cycles of therapy are planned.
Interventions
DRUGMitoxantrone Hydrochloride Liposome
Drug: Mitoxantrone hydrochloride liposome (20 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.
DRUGRituximab
Drug: Rituximab (375 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.
DRUGLenalidomide
Drug: Lenalidomide (25 mg) will be taken orally from day 1 to day 8 of each 28-day cycle.
Sponsors
CSPC Ouyi Pharmaceutical Co., Ltd.
Jianfeng Zhou
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1.Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF); * 2.60-75 years old; * 3.Expected survival ≥ 3 months; * 4.Subjects with histologically confirmed diagnosis of relapsed and refractory diffuse large B-cell lymphoma who have received at least 4 cycles of first-line chemotherapy including rituximab and anthracyclines; 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; * 5.Subjects who are not eligible for transplantation or do not plan to undergo transplantation at the beginning of the study; * 6.ECOG Performance Status: 0-2; * 7.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; * 8.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); * 9.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 within 4 weeks or 5 T1/2s before the first administration of the study drugs; 4. Subjects who received lenalidomide. * 2.Subjects with refractory lymphoma meet one of the following criteria: 1) Tumors assessed as SD/PD after ≥2 lines of chemotherapy; 2) Subjects relapse within 6 months after transplantation. * 3.Hypersensitivity to any study drug or its components; * 4.Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.) * 5.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. * 6.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) * 7.Baseline B-type pro-brain natriuretic peptide (NT-proBNP) \> 1800pg/ml, troponin I (cTnI) \> ULN of our center, and the retest data is still higher than the above range after three days; * 8.Human immunodeficiency virus (HIV) infection (HIV antibody positive); * 9.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); * 10.Subjects suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment; * 11.Unsuitable subjects for this study determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | through study completion, an average of 2 year | To investigate the preliminary antitumor efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | through study completion, an average of 2 year | To investigate the preliminary antitumor efficacy |
| Duration of relief (DOR) | through study completion, an average of 2 year | To investigate the preliminary antitumor efficacy |
| Disease Control Rate (DCR) | through study completion, an average of 2 year | To investigate the preliminary antitumor efficacy |
| Best of response (BOR) | 6-8 weeks | To investigate the preliminary antitumor efficacy |
| Safety endpoint: The incidence and severity of AE and SAE Safety endpoint: The incidence and severity of AE and SAE Safety endpoint:The incidence and severity of AE and SAE | through study completion, an average of 2 year | To identify the incidence and severity of AE and SAE (NCI CTCAE v5.0) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy assessed by IgNGS | through study completion, an average of 2 year | Efficacy assessed by IgNGS |
| Other metrics that researchers are interested | through study completion, an average of 2 year | Other metrics that researchers are interested |
Countries
China
Contacts
Primary Contactliang Huang
Outcome results
None listed