Mitoxantrone Hydrochloride Liposome Combined With Rituximab and Lenalidomide (M+R2) in Patients With Relapsed and Refractory Diffuse Large B-Cell Lymphoma

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Prospective, Single-arm, Multicenter Clinical Study of Mitoxantrone Hydrochloride Liposome Combined With Rituximab and Lenalidomide in the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05575973
• Other study ID #: CSPC-DED-DLBCL-K03
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 10, 2022
• Est. completion date: October 2025

Study information

• Verified date: October 2022
• Source: Huazhong University of Science and Technology
• Contact: liang Huang
• Phone: 027-83665555
• Email: lhuang[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: October 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Mitoxantrone Hydrochloride Liposome
Drug: Mitoxantrone hydrochloride liposome (20 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.
• Rituximab
Drug: Rituximab (375 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.
• Lenalidomide
Drug: Lenalidomide (25 mg) will be taken orally from day 1 to day 8 of each 28-day cycle.

Locations

Country	Name	City	State
China	Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Jianfeng Zhou	CSPC Ouyi Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy assessed by IgNGS	Efficacy assessed by IgNGS	through study completion, an average of 2 year
Other	Other metrics that researchers are interested	Other metrics that researchers are interested	through study completion, an average of 2 year
Primary	Objective response rate (ORR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Secondary	Progression free survival (PFS)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Secondary	Duration of relief (DOR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Secondary	Disease Control Rate (DCR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Secondary	Best of response (BOR)	To investigate the preliminary antitumor efficacy	6-8 weeks
Secondary	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	To identify the incidence and severity of AE and SAE (NCI CTCAE v5.0)	through study completion, an average of 2 year