Clinical trial NCT05458180: CMOEP in the Treatment of Untreated Peripheral T-cell Lymphoma
Official title: Phase I Cinical Sudy of Lposomal Mitoxantrone Hydrochloride Combined With Cyclophosphamide, Vincristine, Etoposide and Prednisone (CMOEP) in Previously Untreated Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Peripheral T-cell Lymphoma
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
Collaborators: name: CSPC Ouyi Pharmaceutical Co., Ltd.
First posted: 2022-07-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Subjects fully understand and voluntarily participate in this study and sign informed consent.
2. Age ≥18, ≤65years, no gender limitation.
3. Expected survival ≥ 3 months.
4. 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.
5. 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.
6. 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.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
8. 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.
9. 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:

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).
2. Hypersensitivity to any study drug or its components.
3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)
4. 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.
5. 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).
6. Human immunodeficiency virus (HIV) infection (HIV antibody positive).
7. 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.
8. Patients with primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma.
9. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures.
10. Unsuitable subjects for this study determined by the investigator.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Cycle 1 (21 days)
Secondary outcomes:
measure: Dose limited toxicities (DLTs)
timeFrame: Cycle 1 (21 days)
measure: The incidence of AE and SAE
timeFrame: Up to 28 days after the last patient complete his study therapy
measure: Objective response rate (ORR)
timeFrame: Up to 1 year
measure: Complete response rate (CRR)
timeFrame: Up to 1 year
measure: Progression-free survival（PFS）
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Insititute & Hospital
state: Tianjin
Study officials:
References: