R-CMOP in Patients With Newly Diagnosed Diffuse Large B-cell Lymphoma

A Multicenter, Prospective Phase I/II Trial to Evaluate the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome in Combination With Cyclophosphamide, Vincristine, Prednisone, and Rituximab in Patients With Newly Diagnosed DLBCL

This is a prospective clinical study to evaluate the safety and efficacy of R-CMOP in patients with newly diagnosed diffuse large B-cell lymphoma

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome; Drug: Rituximab (R); Drug: Cyclophosphamide (CTX); Drug: Vincristin; Drug: Prednisolone

Detailed Description

This is an open, multicenter, prospective phase I/II clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome injection in combination with cyclophosphamide, vincristine, prednisone, and rituximab (R-CMOP) in patients with newly diagnosed diffuse large B-cell lymphoma. The study is divided into two parts. The first part uses a 3+3 dose-escalation design, in which mitoxantrone hydrochloride liposome injection in the R-CMOP regimen will be administered at three different doses: 16 mg/m², 18 mg/m², and 20 mg/m², to determine the recommended Phase 2 dose (RP2D). The second part follows a single-arm design to evaluate the efficacy and safety of the R-CMOP regimen, with mitoxantrone hydrochloride liposome injection administered at the RP2D. Each cycle consists of 21 days. A maximum of 6 cycles of therapy are planned.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wei Liu; Phone Number: +86-022-23608461; Email: liuwei@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Disease Hospital
      • Principal Investigator: Wei Liu, MD
      • Contact: Wei Liu, MD; Phone Number: 86-022-23908463; Email: liuwei@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years;
2. Histologically confirmed newly diagnosed diffuse large B-cell lymphoma;
3. Patients must have been untreated, including chemotherapy, targeted therapy, immunotherapy, radiotherapy;
4. There must be at least one measurable lesion per the Lugano2014 criteria；
5. For lymph lesion, the long axis must be greater than 1.5cm with 18F-deoxyglucose (18FDG) PET-CT positive；
6. Ann Arbor stages II-IV；
7. ECOG score 0~2；
8. Expected survival time ≥3 months;

9. a.)Patients should meet the following requirements and must not have received treatment with cell growth factors or blood products within 14 days prior to the hematology test: Absolute value of neutrophils ≥ 1.5 × 10^9/L; Platelet ≥ 75 × 10^9/L; Hemoglobin≥80g/L. For patients with bone marrow involvement of lymphoma, the requirements are adjusted as follows: Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L; Platelet count ≥ 50 × 10^9/L; Hemoglobin level ≥ 75 g/L.

   b.)Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST and ALT ≤ 5 × ULN for patients with liver involvement. Total bilirubin ≤1.5 × ULN (≤ 3 × ULN for patients with Gilbert syndrome); c.)Creatinine clearance ≥ 50 mL/min or serum creatinine ≤ 2× ULN; d.)Coagulation function: prothrombin time or activated partial thromboplastin time≤ 1.5 × ULN, and international normalized ratio ≤ 1.5;

10. Female patients of childbearing age must have a negative pregnancy test at the time of enrollment within one week. And patients must agree to use an effective method of contraception from the study initiation until at least 12 months after the last treatment;
11. Able to understand and comply with the study, and voluntarily sign informed consent; -

Exclusion Criteria:

1. Primary central nervous system DLBCL, Primary testicular large B-cell lymphoma, Primary mediastinal (thymic) large B-cell lymphoma, Lymphomatoid granulomatosis, ALK-positive large B-cell lymphoma, Plasmablastic lymphoma, HHV8-positive DLBCL, Primary effusion lymphoma, Intravascular large B-cell lymphoma, B-cell lymphoma unclassifiable between DLBCL and classical Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, and High-grade B-cell lymphoma；
2. transformed indolent lymphoma ;
3. Patients with active central nervous system involvement;
4. History of hematopoietic stem cell transplantation;
5. Have received prior anti-lymphoma treatment, excluding short-term or low-dose corticosteroids.;
6. Used any NMPA-approved anticancer herbal medicines or proprietary Chinese medicines within 14 days prior to the first dose;
7. History of allergy and contraindications to the same class and excipients of the experimental drug;
8. Participating in any other intervention clinical trials within 4 weeks prior to the first dose except for participation in an observational (non-interventional) clinical study or the follow-up phase of an interventional study;
9. Active bacterial or viral infections requiring systemic or intravenous drug treatment.
10. History of immunodeficiency, including anti-HIV positive;
11. Active hepatitis B and C infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than the Upper limit of normal(ULN); Hepatitis C virus antibody positive and hepatitis C virus RNA higher than the Upper limit of normal);
12. syphilis infection;
13. Individuals with an underlying medical condition, alcohol or drug abuse or dependence that impedes study drug administration or interferes with interpretation of study drug toxicity and AE, or results in inadequate or reduced adherence to the study;

14. Patients with interstitial lung disease that requires treatment; 15: A history of severe cardiovascular disease, including but not limited to:

    1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, or second to third-degree atrioventricular (AV) block;
    2. A mean QTcF interval longer than 450 ms, based on three 12-lead ECGs taken at rest;
    3. Acute coronary syndrome, congestive heart failure, stroke, or any other Grade 3 or higher cardiovascular event occurring within 6 months prior to the first dose of therapy;
    4. NYHA functional class ≥ II or left ventricular ejection fraction (LVEF)lower than 50%;
    5. Any factors that increase the risk of QTc prolongation or arrhythmias, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome or unexplained sudden death in a first-degree relative under the age of 40, or concurrent use of any medications known to prolong the QT interval;
    6. uncontrolled hypertension;

16. History of other malignant tumor within 2 years, except for DLBCL in this trial or resected locally cancer that has been cured (e.g.basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast); 17. No psychological, spiritual potentially hampering compliance with the study protocol and follow-up schedule; 18. Women who are pregnant or breastfeeding; 19. Any other reasons deemed by the investigator to render the participant unsuitable for inclusion in this clinical trial.

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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: R-CMOP; R-CMOP regimen includes rituximab (R), cyclophosphamide (C), mitoxantrone hydrochloride liposome injection (M), vincristine (O), and prednisone (P). The regimen will be administered every 3 weeks, for a maximum of 6 cycles.	Drug: Mitoxantrone Hydrochloride Liposome; assigned dose according to the 3+3 dose-escalation design in part 1, RP2D in part 2, D2; Drug: Rituximab (R); 375mg/m2, D2; Drug: Cyclophosphamide (CTX); 750mg/m2, D2; Drug: Vincristin; 1.2mg/m2, maximum 2mg， D2; Drug: Prednisolone; 60mg/m2, D2-6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I:Maximum tolerated dose (MTD)	Maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride in R-CMOP	Through the last patient complete his DLT observation, assessed up to 21 days
Phase I: Recommended phaseII dose (RP2D)	The Recommended Phase II Dose (RP2D) is defined as the optimal dose of liposomal mitoxantrone hydrochloride for use in Phase II trials, as determined by the outcomes of the Phase I study.	Through the last patient complete his DLT observation, assessed up to 21 days
Phase II:Complete remission rate (CRR)	Response is assessed according to the lugano criteria	up to 2 years
Phase I: Dose limited toxicities (DLTs)	adverse events defined as DLT events per protocol	Through the last patient complete his DLT observation, assessed up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: The incidence rates of adverse events (AEs)	AE or severe adverse events (SAE) occur since the first dose of therapy is given	up to 2 years
Phase I: Objective response rate (ORR)	Response is assessed according to the lugano criteria	up to 2 years
Phase I: Complete remission rate (CRR)	Response is assessed according to the lugano criteria	up to 2 years
Phase II: Overall response rate (ORR)	Response is assessed according to the lugano criteria	up to 2 years
Phase II: Partial response rate (PRR)	Response is assessed according to the lugano criteria	up to 2 years
Phase II: Duration of response (DOR)	DOR was defined as the time from first complete response or partial response to disease progression or death from any causes.	up to 2 years
Phase II: Progression-free survival (PFS)	From the date of the first dose of therapy is given until disease progression or death from any cause.	up to 2 years
Phase II: Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause	up to 2 years
Phase II: Disease-free survival (DFS)	From the date of achieving a complete response until disease progression or death from any cause.	up to 2 years
Phase II: Event-free survival (EFS)	From the date of the first dose of therapy is given until disease progression, death , or the initiation of a new treatment regimen.	up to 2 years
Phase II: The incidence rates of adverse events (AEs)	AE or severe adverse events (SAE) occur since the first dose of therapy is given	up to 2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Lugui Qiu, Professor, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: September 5, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Diffuse Large B-cell Lymphoma; Mitoxantrone hydrochloride liposome injection
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Alkaloids; Polycyclic Compounds; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Antibodies, Monoclonal, Murine-Derived; Rituximab; Prednisolone; Cyclophosphamide; Vincristine
• Other Study ID Numbers: IIT2024014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No