CMOEP in the Treatment of Untreated Peripheral T-cell Lymphoma

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Lposomal mitoxantrone hydrochloride,Cyclophosphamide,Vincristine,Etoposide and Prednisone(CMOEP)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huilai Zhang, MD；PhD; Phone Number: 086-02223340123; Email: zhlwgq@126.com
• Study Contact Backup: Name: Jingwei Yu, MD；PhD; Phone Number: 086-02223340123; Email: jingweiyu@pku.org.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Insititute & Hospital
      • Contact: Zhang Huilai, PHD; Phone Number: 086-02223340123; Email: zhlwgq@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 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 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.

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: CMOEP; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 7, 2022
• Primary Completion (Anticipated): December 15, 2024
• Study Completion (Anticipated): April 15, 2025

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: June 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, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Prednisone; Vincristine; Mitoxantrone
• Other Study ID Numbers: CSPC-DED-PTCL-K02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual patient data will be shared with other researchers

Drug and device information, study documents

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