GVM±R in Patients With Relapsed or Refractory Aggressive NHL

NCT05299164 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: IIT2022003
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, dose-escalation clinical study to evaluate the safety and efficacy of GVM±R in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL).

Conditions

Non Hodgkin Lymphoma

Keywords

GVM±R; liposomal mitoxantrone hydrochloride

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride in GVM±R

  Through the last patient complete his DLT observation, assessed up to 21 days

Secondary Outcomes (5)

• Dose limited toxicities (DLTs)

  Through the last patient complete his DLT observation, assessed up to 21 days

• The incidence rates of AE and SAE

  up to 28 days after the last patient complete his study therapy

• Objective response rate (ORR)

  up to 2 years

• Complete response rate (CRR)

  : up to 2 years

• progression-free survival（PFS）

  up to 2 years

Study Arms (4)

Liposomal mitoxantrone hydrochloride 16 mg/m^2 (with a caret included)

EXPERIMENTAL

Drug: Liposomal Mitoxantrone Hydrochloride dose level 1

Liposomal mitoxantrone hydrochloride 18 mg/m^2 (with a caret included)

EXPERIMENTAL

Drug: Liposomal Mitoxantrone Hydrochloride dose level 2

Liposomal mitoxantrone hydrochloride 20 mg/m^2 (with a caret included)

EXPERIMENTAL

Drug: Liposomal Mitoxantrone Hydrochloride dose level 3

Liposomal mitoxantrone hydrochloride 22 mg/m^2 (with a caret included)

EXPERIMENTAL

Drug: Liposomal Mitoxantrone Hydrochloride dose level 4

Interventions

Liposomal Mitoxantrone Hydrochloride dose level 1 DRUG

Liposomal Mitoxantrone Hydrochloride 16 mg/m\^2 (with a caret included) on day 1, every 3 weeks; Gemcitabine (800 mg/m\^2) on day 1,8, every 3 weeks; Vinorelbine (25mg/m\^2) on day 1,8, every 3 weeks; Rituximab (375mg/m\^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;

Liposomal mitoxantrone hydrochloride 16 mg/m^2 (with a caret included)

Liposomal Mitoxantrone Hydrochloride dose level 2 DRUG

Liposomal Mitoxantrone Hydrochloride 18 mg/m\^2 (with a caret included) on day 1, every 3 weeks; Gemcitabine (800 mg/m\^2) on day 1,8, every 3 weeks; Vinorelbine (25mg/m\^2) on day 1,8, every 3 weeks; Rituximab (375mg/m\^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;

Liposomal mitoxantrone hydrochloride 18 mg/m^2 (with a caret included)

Liposomal Mitoxantrone Hydrochloride dose level 3 DRUG

Liposomal Mitoxantrone Hydrochloride 20 mg/m\^2 (with a caret included) on day 1, every 3 weeks; Gemcitabine (800 mg/m\^2) on day 1,8, every 3 weeks; Vinorelbine (25mg/m\^2) on day 1,8, every 3 weeks; Rituximab (375mg/m\^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;

Liposomal mitoxantrone hydrochloride 20 mg/m^2 (with a caret included)

Liposomal Mitoxantrone Hydrochloride dose level 4 DRUG

Liposomal Mitoxantrone Hydrochloride 22 mg/m\^2 (with a caret included) on day 1, every 3 weeks; Gemcitabine (800 mg/m\^2) on day 1,8, every 3 weeks; Vinorelbine (25mg/m\^2) on day 1,8, every 3 weeks; Rituximab (375mg/m\^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;

Liposomal mitoxantrone hydrochloride 22 mg/m^2 (with a caret included)

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 the informed consent
• Age ≥18, ≤70years, no gender limitation
• Expected survival ≥ 3 months;
• Histologically confirmed diagnosis of aggressive NHL.
• Subjects with relapsed or refractory NHL. Relapsed disease is defined as the disease relapsing after CR or PR, and the duration of prior response is more than 6 months. Refractory disease can be confirmed if any of the following conditions are met: 1) no PR or CR has been obtained after previous treatment; 2) CR / PR was achieved after prior therapy, but recurred within 6 months; 3) Recurrence after hematopoietic stem cell transplantation.
• 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;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) : 0-1
• The following baseline laboratory criteria are required: 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.

You may not qualify if:

• The subject had previously received any of the following anti-tumor treatments:
• Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
• 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);
• Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs within 4 weeks before the first administration of the study drugs;
• Subjects who received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days of the first administration of study drugs;
• Hypersensitivity to any study drug or its components;
• Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)
• Heart function and disease meet one of the following conditions:
• Long QTc syndrome or QTc interval \> 480 ms;
• Complete left bundle branch block, grade II or III atrioventricular block;
• Serious and uncontrolled arrhythmias requiring drug treatment;
• New York Heart Association grade ≥ III;
• Cardiac ejection fraction (LVEF)# 50%;
• 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.
• \. Hepatitis B and hepatitis C active infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than 1x103 copy/mL; hepatitis C virus RNA high than 1x103 copy/mL) 10. Human immunodeficiency virus (HIV) infection (defined as HIV antibody positive) 11. Patients with other malignant tumors, except for effectively controlled non- melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ or other tumors without treatment during the past 5 years. 12. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures; 13. Unsuitable subjects for this study determined by the investigator.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• CSPC Ouyi Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

Tianjin, Please Select, 300020, China

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Wei Liu

  Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 dose-escalation

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 28, 2022
• Study Start: May 15, 2022
• Primary Completion: December 18, 2023
• Study Completion: December 31, 2025
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)