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

Peripheral T Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04548700
• Other study ID #: HE071-CSP-011
• Status: Terminated
• Phase: Phase 1
• Start date: December 24, 2020
• Est. completion date: November 30, 2023

Study information

• Verified date: August 2020
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: November 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 (ß-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

Related Conditions & MeSH terms

• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma
• Treatment-naïve

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-finding stage: The incidence of dose limited toxicities (DLTs)	To identify the DLTs	Cycle 1 (28 days)
Primary	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
Primary	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	Dose-finding stage: complete response(CR) rate	To investigate the preliminary antitumor efficacy	up to 24 weeks
Secondary	Dose-finding stage: duration of complete response(DoCR)	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Secondary	Dose-finding stage: overall response rate (ORR)	To investigate the preliminary antitumor efficacy	up to 24 weeks
Secondary	Dose-finding stage: progression-free survival(PFS)	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Secondary	Dose-finding stage:the pharmacokinetic parameters Cmax	To investigate the PK characteristics	Cycle 1 to Cycle 6(each cycle is 28 days)
Secondary	Dose-finding stage:the pharmacokinetic parameters AUC0-t	To investigate the PK characteristics	Cycle 1 to Cycle 6(each cycle is 28 days)
Secondary	Dose-expansion stage: CR rate	To investigate the preliminary antitumor efficacy	up to 24 weeks
Secondary	Dose-expansion stage: DoCR	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Secondary	Dose-expansion stage: ORR	To investigate the preliminary antitumor efficacy	up to 18-24 weeks
Secondary	Dose-expansion stage: PFS	To investigate the preliminary antitumor efficacy	Throughout study completion,an average of 18 months
Secondary	Dose-expansion stage: the pharmacokinetic parameters Cmax	To investigate the PK characteristics	Cycle 1(each cycle is 21or28 days)
Secondary	Dose-expansion stage: the pharmacokinetic parameters AUC0-t	To investigate the PK characteristics	Cycle 1(each cycle is 21or28 days)