CMOEP in the Treatment of Untreated Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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This is a prospective, single arm, multicenter, dose-escalation clinical study to evaluate the safety and efficacy of CMOEP in patients with untreated Peripheral T-cell Lymphoma.

Detailed Description
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This is a single arm, multicenter, dose-escalation study which mainly explores the dose limiting toxicity (DLT) of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine, Etoposide and Prednisone（CMOEP） in patients with untreated Peripheral T-cell Lymphoma. Liposomal mitoxantrone hydrochloride will be given on day 1 at three different doses (15 mg/m2, 18 mg/m2, 20 mg/m2) and be combined with Cyclophosphamide, Vincristine, Etoposide and Prednisone. The dose limited toxicity (DLT) will be evaluated after the first cycle of therapy. A maximum of 6 cycles of therapy are planned.

Official Title
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Phase I Cinical Sudy of Lposomal Mitoxantrone Hydrochloride Combined With Cyclophosphamide, Vincristine, Etoposide and Prednisone (CMOEP) in Previously Untreated Peripheral T-cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Lposomal mitoxantrone hydrochloride,Cyclophosphamide,Vincristine,Etoposide and Prednisone(CMOEP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects fully understand and voluntarily participate in this study and sign informed consent. Age ≥18, ≤65years, no gender limitation. Expected survival ≥ 3 months. Histologically confirmed diagnosis of Peripheral T-cell lymphoma： 1) Peripheral T-cell lymphoma unspecified (ptcl-NOS) 2) Angioimmunoblastic T-cell lymphoma (AITL) 3) Anaplastic large T-cell lymphoma (ALCL), ALK+ 4) Anaplastic large T-cell lymphoma (ALCL), ALK- 5) Other subtypes of PTCL that the investigator think can be included in the group. No previous treatment for PTCL, including chemotherapy, targeted therapy, immunotherapy, local radiotherapy for lymphoma (except for local radiotherapy to alleviate tumor related symptoms), surgical treatment. Subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length and diameter should be > 1.5cm; For non-lymph node lesions, the length and diameter should be > 1.0cm. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1. The following baseline laboratory criteria are required: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count (PLT) ≥75×10^9/L, Hemoglobin(HB)≥ 90 g/L. Total Serum creatinine (Scr) ≤1.5X upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN, bilirubin (TBIL)≤1.5X ULN. Exclusion Criteria: 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). Hypersensitivity to any study drug or its components. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.) 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 ≥ II;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. Hepatitis B and hepatitis C active infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than 1x10^3 copy/mL; hepatitis C virus RNA high than 1x10^3 copy/mL). Human immunodeficiency virus (HIV) infection (HIV antibody positive). Patients with other malignant tumors, except for effectively controlled non melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ and other tumor during the past 5 years. Patients with primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures. Unsuitable subjects for this study determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMOEP<br>dose-escalation： Untreated Peripheral T-cell Lymphoma Patients will receive sequentially higher doses of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine, Etoposide and Prednisone for 6 cycles (planned) (21 days per cycle). The initial dose of liposomal mitoxantrone hydrochloride is 15 mg/m2. | Drug: Lposomal mitoxantrone hydrochloride,Cyclophosphamide,Vincristine,Etoposide and Prednisone(CMOEP)<br>* Drug: Liposomal mitoxantrone hydrochloride (15 mg/m2, 18 mg/m2, 20 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle. Drug: Cyclophosphamide (750 mg/ m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle. Drug: Vincristine (1.4mg/ m2，Max dose 2mg) will be administered by an intravenous injection on day 1of each 21-day cycle. Drug: Etoposide (60 mg/ m2) will be administered by an intravenous infusion on day 1-3 of each 21-day cycle. Drug: Prednisone (100 mg) will be taken orally from day 1-5 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride in CMOEP | Cycle 1 (21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicities (DLTs) | Adverse events (AE) defined as DLT events per protocol | Cycle 1 (21 days) | 
| The incidence of AE and SAE | AE or severe adverse events (SAE) occur since the first dose of therapy is given | Up to 28 days after the last patient complete his study therapy | 
| Objective response rate (ORR) | Response is assessed according to the lugano criteria | Up to 1 year | 
| Complete response rate (CRR) | Response is assessed according to the lugano criteria | Up to 1 year | 
| Progression-free survival（PFS） | From the date of the first dose of therapy is given until disease progression, death | Up to 1 year |