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
Overview
- Phase
- Phase 1
- Intervention
- Mitoxantrone Hydrochloride Liposome
- Conditions
- Diffuse Large B-cell Lymphoma
- Sponsor
- Institute of Hematology & Blood Diseases Hospital, China
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- Phase I:Maximum tolerated dose (MTD)
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years;
- •Histologically confirmed newly diagnosed diffuse large B-cell lymphoma;
- •Patients must have been untreated, including chemotherapy, targeted therapy, immunotherapy, radiotherapy;
- •There must be at least one measurable lesion per the Lugano2014 criteria；
- •For lymph lesion, the long axis must be greater than 1.5cm with 18F-deoxyglucose (18FDG) PET-CT positive；
- •Ann Arbor stages II-IV；
- •ECOG score 0\~2；
- •Expected survival time ≥3 months;
- •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;
Exclusion Criteria
- •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；
- •transformed indolent lymphoma ;
- •Patients with active central nervous system involvement;
- •History of hematopoietic stem cell transplantation;
- •Have received prior anti-lymphoma treatment, excluding short-term or low-dose corticosteroids.;
- •Used any NMPA-approved anticancer herbal medicines or proprietary Chinese medicines within 14 days prior to the first dose;
- •History of allergy and contraindications to the same class and excipients of the experimental drug;
- •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;
- •Active bacterial or viral infections requiring systemic or intravenous drug treatment.
- •History of immunodeficiency, including anti-HIV positive;
Arms & Interventions
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.
Intervention: Mitoxantrone Hydrochloride Liposome
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.
Intervention: Rituximab (R)
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.
Intervention: Cyclophosphamide (CTX)
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.
Intervention: Vincristin
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.
Intervention: Prednisolone
Outcomes
Primary Outcomes
Phase I:Maximum tolerated dose (MTD)
Time Frame: Through the last patient complete his DLT observation, assessed up to 21 days
Maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride in R-CMOP
Phase I: Recommended phaseII dose (RP2D)
Time Frame: Through the last patient complete his DLT observation, assessed up to 21 days
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.
Phase II:Complete remission rate (CRR)
Time Frame: up to 2 years
Response is assessed according to the lugano criteria
Phase I: Dose limited toxicities (DLTs)
Time Frame: Through the last patient complete his DLT observation, assessed up to 21 days
adverse events defined as DLT events per protocol
Secondary Outcomes
- Phase I: The incidence rates of adverse events (AEs)(up to 2 years)
- Phase I: Objective response rate (ORR)(up to 2 years)
- Phase I: Complete remission rate (CRR)(up to 2 years)
- Phase II: Overall response rate (ORR)(up to 2 years)
- Phase II: Partial response rate (PRR)(up to 2 years)
- Phase II: Duration of response (DOR)(up to 2 years)
- Phase II: Progression-free survival (PFS)(up to 2 years)
- Phase II: Overall survival (OS)(up to 2 years)
- Phase II: Disease-free survival (DFS)(up to 2 years)
- Phase II: Event-free survival (EFS)(up to 2 years)
- Phase II: The incidence rates of adverse events (AEs)(up to 2 years)