Liposomal Mitoxantrone Hydrochloride Injection,Cyclophosphamide, Vincristine and Prednisone in the Treatment of PTCL

Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Liposomal Mitoxantrone Hydrochloride Injection Combined With Cyclophosphamide, Vincristine and Prednisone in the Treatment of Untreated PTCL

This is a multicentre, open-label, single-arm, phase Ib clinical study to evaluate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with peripheral T cell lymphoma (PTCL).

Study Overview

• Status: Terminated
• Conditions: Peripheral T Cell Lymphoma; Treatment-naïve
• Intervention / Treatment: Drug: Dose-finding stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone; Drug: Dose-expansion stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone

Detailed Description

The study is to investigate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with PTCL by conducting in two stages, Dose-finding stage and Dose-expansion stage.In Dose-finding stage, patients with treatment-naïve PTCL will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride ranging from 12 to 18 mg/m2 plus Cyclophosphamide, Vincristine and Prednisone (28 days per cycle). The dose escalation will follow the classic 3+3 design. The recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined according to the Dose-finding results. In Dose-expansion stage, additional patients will be recruited into two groups, the Q4W group（28 days per cycle）and the Q3W group（21 days per cycle）, to receive liposomal mitoxantrone hydrochloride at the RP2D combined with Cyclophosphamide, Vincristine and Prednisone. All patients will receive the treatment for the planned 6 cycles or until disease progression or unacceptable drug-related adverse events.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects fully understand and voluntarily participate in this study and sign informed consent
2. Age ≥18, ≤70years, no gender limitation
3. Histologically confirmed diagnosis of treatment-naïve PTCL. Eligible histologies are limited to the following: Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS),Angioimmunoblastic T-cell lymphoma (AITL), ALK -positive Anaplastic Large cell Lymphoma（ALCL）, ALK-negative ALCL; Other PTCL that investigators consider to be appropriate to be enrolled
4. PTCL with fluorodeoxyglucose (FDG) avidity that can be evaluated by PET/CT
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
6. The following required baseline laboratory data: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLT) ≥75×109/L, Hemoglobin(HB)≥ 80g/L, Total bilirubin (TBIL) ≤1.5X upper limit of normal (ULN) , Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN , Serum creatinine (Scr) ≤1.5X ULN
7. Females of childbearing potential must have a negative serum beta human chorionic gonadotrophin (β-hCG) pregnancy test result prior to enrollment and must agree to use an effective contraception method for the duration of the study treatment and 12 months after the last dose of study therapy
8. Males of reproductive potential must agree to use an effective contraceptive method for the duration of the study treatment and 12 months after the last dose of study therapy

Exclusion Criteria:

1. Current diagnosis of any of the following: extranodal natural killer/T-cell lymphoma, nasal type(NKTCL), Mycosis fungoides (MF)/ Sézary syndrome (SS), Primary cutaneous ALCL，and Adult T-cell leukemia/lymphoma
2. Leukemic phase of lymphoma (≥20% lymphoma cell in the bone marrow), or central nervous system (CNS) involvement, or hemophagocytic syndrome
3. Life expectancy < 6 months
4. History of allergy to anthracyclines or liposomes
5. History of contraindications to cyclophosphamide, vincristine or prednisone
6. Prior anti-lymphoma therapy except short-term or low-dose corticosteroid treatment
7. Impaired cardiac function or significant cardiac disease
8. Positive test results for HBsAg antigen and HBV-DNA, or hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody
9. Major surgery within 4～6weeks prior to screening. Or have a surgical schedule during the study
10. A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator
11. Uncontrolled hypertension at screening
12. Uncontrolled diabetes at screening
13. History of active visceral hemorrhage in the recent 3 months prior to screening
14. History of other tumors in the past five years prior to screening. Patients with curable tumors (such as skin basal cell carcinoma, carcinoma in situ of the cervix or of the breast, intramucosal carcinoma in situ of the gastrointestinal tract or localized prostate cancer) could be enrolled after completely cured
15. History of solid organ transplantation
16. Known psychiatric disorders or cognitive disorder
17. Known alcohol or drug abuse
18. Pregnant or breastfeeding women
19. Not suitable for this study as determined by the investigator due to other reasons

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: Dose-finding and dose-expansion; Dose-finding stage: Patients with treatment-naïve PTCL will receive sequentially higher doses of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone for 6 cycles (planned) (28 days per cycle). The initial dose of liposomal mitoxantrone hydrochloride is 12 mg/m2. Dose-expansion stage: Patients with treatment-naïve PTCL will receive liposomal mitoxantrone hydrochloride at RP2D in combination with Cyclophosphamide, Vincristine and Prednisone for 6 cycles (planned) (28 or 21 days per cycle).

Drug: Dose-finding stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone; Drug: Liposomal mitoxantrone hydrochloride (12 mg/m2, 15 mg/m2, 18 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle. Drug: Cyclophosphamide (750 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle. Drug: Vincristine (1.4 mg/m2 with 2 mg as the maximum dose) will be administered by an intravenous injection on day 1 of each 28-day cycle. Drug: Prednisone (100 mg/d) will be taken orally from day 1 to day 5 of each 28-day cycle.; Other Names: Part1; Drug: Dose-expansion stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone; Drug: Liposomal mitoxantrone hydrochloride (at RP2D) will be administered by an intravenous infusion on day 1 of each 28- or 21-day cycle. Drug: Cyclophosphamide (750 mg/m2) will be administered by an intravenous infusion on day 1 of each 28- or 21-day cycle. Drug: Vincristine (1.4 mg/m2 with 2 mg as the maximum dose) will be administered by an intravenous injection on day 1 of each 28- or 21-day cycle. Drug: Prednisone (100 mg/d) will be taken orally from day 1 to day 5 of each 28- or 21-day.; Other Names: Part2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-finding stage: The incidence of dose limited toxicities (DLTs)	To identify the DLTs	Cycle 1 (28 days)
Dose-finding stage:The incidence of AE and SAE	To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams	up to 24 weeks
Dose-expansion stage: The incidence of AE and SAE	To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams	up to 18-24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-finding stage: complete response(CR) rate	To investigate the preliminary antitumor efficacy	up to 24 weeks
Dose-finding stage: duration of complete response（DoCR）	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Dose-finding stage: overall response rate (ORR)	To investigate the preliminary antitumor efficacy	up to 24 weeks
Dose-finding stage: progression-free survival（PFS）	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Dose-finding stage：the pharmacokinetic parameters Cmax	To investigate the PK characteristics	Cycle 1 to Cycle 6(each cycle is 28 days)
Dose-finding stage：the pharmacokinetic parameters AUC0-t	To investigate the PK characteristics	Cycle 1 to Cycle 6(each cycle is 28 days)
Dose-expansion stage: CR rate	To investigate the preliminary antitumor efficacy	up to 24 weeks
Dose-expansion stage: DoCR	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Dose-expansion stage: ORR	To investigate the preliminary antitumor efficacy	up to 18-24 weeks
Dose-expansion stage: PFS	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Dose-expansion stage: the pharmacokinetic parameters Cmax	To investigate the PK characteristics	Cycle 1(each cycle is 21or28 days)
Dose-expansion stage: the pharmacokinetic parameters AUC0-t	To investigate the PK characteristics	Cycle 1(each cycle is 21or28 days)

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Huiqiang Huang, Doctor, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: August 28, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: August 1, 2020

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; Prednisone; Vincristine; Mitoxantrone
• Other Study ID Numbers: HE071-CSP-011

Drug and device information, study documents

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