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

Phase 1

Terminated

• Conditions: Treatment-naïve; Peripheral T Cell Lymphoma

• Registration Number: NCT04548700
• Lead Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Brief Summary

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).

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 Timeline

• Status Verified: 2020-08
• Study First Submitted: 2020-08-28
• Study First Submitted QC: 2020-09-09
• Study First Posted: 2020-09-14
• Study Start: 2020-12-24
• Primary Completion: 2023-06-30
• Study Completion: 2023-11-30
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 38

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China