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

NCT ID: NCT05575973

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-10
• Study Completion Date: 2025-10-31

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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mitoxantrone hydrochloride liposome

Patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) will receive sequentially mitoxantrone hydrochloride liposome in combination with rituximab and lenalidomide for up to 6 cycles (28 days per cycle).

Group Type: EXPERIMENTAL

Mitoxantrone Hydrochloride Liposome

Intervention Type: DRUG

Drug: Mitoxantrone hydrochloride liposome (20 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.

Rituximab

Intervention Type: DRUG

Drug: Rituximab (375 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.

Lenalidomide

Intervention Type: DRUG

Drug: Lenalidomide (25 mg) will be taken orally from day 1 to day 8 of each 28-day cycle.

Interventions

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.

Intervention Type: DRUG

Rituximab

Drug: Rituximab (375 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle.

Intervention Type: DRUG

Lenalidomide

Drug: Lenalidomide (25 mg) will be taken orally from day 1 to day 8 of each 28-day cycle.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSPC Ouyi Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Jianfeng Zhou

OTHER

Sponsor Role: lead

Responsible Party

Jianfeng Zhou

Director

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Countries

China

Central Contacts

liang Huang

Role: CONTACT

lhuang@tjh.tjmu.edu.cn

027-83665555

Other Identifiers

CSPC-DED-DLBCL-K03

Identifier Type: -

Identifier Source: org_study_id