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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome; Drug: Rituximab; Drug: Lenalidomide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: liang Huang; Phone Number: 027-83665555; Email: lhuang@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Duration of relief (DOR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Disease Control Rate (DCR)	To investigate the preliminary antitumor efficacy	through study completion, an average of 2 year
Best of response (BOR)	To investigate the preliminary antitumor efficacy	6-8 weeks
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy assessed by IgNGS	Efficacy assessed by IgNGS	through study completion, an average of 2 year
Other metrics that researchers are interested	Other metrics that researchers are interested	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Jianfeng Zhou
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 10, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Rituximab; Mitoxantrone
• Other Study ID Numbers: CSPC-DED-DLBCL-K03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No