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

NCT04548700 | Terminated Phase 1

• 1 other identifier: HE071-CSP-011
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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).

Conditions

Treatment-naïve; Peripheral T Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Dose-finding stage: complete response(CR) rate

  up to 24 weeks

• Dose-finding stage: duration of complete response（DoCR）

  Throughout study completion,an average of 18 months

• Dose-finding stage: overall response rate (ORR)

  up to 24 weeks

• Dose-finding stage: progression-free survival（PFS）

  Throughout study completion,an average of 18 months

• Dose-finding stage：the pharmacokinetic parameters Cmax

  Cycle 1 to Cycle 6(each cycle is 28 days)

Study Arms (1)

Dose-finding and dose-expansion

EXPERIMENTAL

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: Dose-expansion stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone

Interventions

Dose-finding stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone DRUG

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.

Also known as: Part1

Dose-finding and dose-expansion

Dose-expansion stage: Liposomal mitoxantrone hydrochloride, Cyclophosphamide, Vincristine and Prednisone DRUG

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.

Also known as: Part2

Dose-finding and dose-expansion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects fully understand and voluntarily participate in this study and sign informed consent
• Age ≥18, ≤70years, no gender limitation
• 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
• PTCL with fluorodeoxyglucose (FDG) avidity that can be evaluated by PET/CT
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• 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
• 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
• 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

You may not qualify if:

• 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
• Leukemic phase of lymphoma (≥20% lymphoma cell in the bone marrow), or central nervous system (CNS) involvement, or hemophagocytic syndrome
• Life expectancy \< 6 months
• History of allergy to anthracyclines or liposomes
• History of contraindications to cyclophosphamide, vincristine or prednisone
• Prior anti-lymphoma therapy except short-term or low-dose corticosteroid treatment
• Impaired cardiac function or significant cardiac disease
• Positive test results for HBsAg antigen and HBV-DNA, or hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody
• Major surgery within 4～6weeks prior to screening. Or have a surgical schedule during the study
• A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator
• Uncontrolled hypertension at screening
• Uncontrolled diabetes at screening
• History of active visceral hemorrhage in the recent 3 months prior to screening
• 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
• History of solid organ transplantation

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

Cyclophosphamide; Vincristine; Prednisone; PART-1 RNA, human

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Huiqiang Huang, Doctor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 14, 2020
• Study Start: December 24, 2020
• Primary Completion: June 30, 2023
• Study Completion: November 30, 2023
• Last Updated: March 7, 2024

Record last verified: 2020-08

Locations

CN (1)