Clinical Study of Liposomal Mitoxantrone Hydrochloride Injection Combined With Pegaspargase in the Treatment of NKTCL

NCT04509466 | Terminated Phase 1

• 1 other identifier: HE071-CSP-012
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentre, open-label, single-arm, phase I/II clinical study to evaluate the safety, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with pegaspargase in patients with extranodal natural killer/T-cell lymphoma, nasal type (NKTCL).

Conditions

Extranodal NK/T-cell Lymphoma, Nasal Type

Outcome Measures

Primary Outcomes (4)

• Part 1：dose limiting toxicities (DLTs)

  The incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams

  Cycle 1 (a cycle = 21 days)

• Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)

  CR rates at the end of chemotherapy

  up to 18 weeks

• Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)

  CR rates at the end of treatment(including chemotherapy and radiation)

  up to 26 weeks

• Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR)

  PR rates at the end of treatment(including chemotherapy and radiation)

  up to 26 weeks

Secondary Outcomes (10)

• Part 1 the preliminary antitumor efficacy: complete response rate (CR)

  up to 26 weeks

• Part 1 the preliminary antitumor efficacy：overall response rate (ORR)

  up to 26 weeks

• Part 1 the preliminary antitumor efficacy:disease control rate (DCR)

  up to 26 weeks

• Part 1: The pharmacokinetic parameters Cmax

  At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)

• Part 1: The pharmacokinetic parameters AUC0-t

  At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)

Study Arms (1)

dose escalation (part 1)

EXPERIMENTAL

dose escalation (part 1):Patients with treatment-naïve, relapsed or refractory extranodal natural killer/T-cell lymphoma (nasal type) will receive liposomal mitoxantrone hydrochloride plus a standard dose of pegaspargase every 21 days (a cycle) for a maximum of 6 cycles. The starting dose of liposomal mitoxantrone hydrochloride is 12mg/m2.dose expansion, treatment-naïve patients (part 2):Patients with treatment-naïve extranodal natural killer/T-cell lymphoma (nasal type) will receive liposomal mitoxantrone hydrochloride at RP2D plus a standard dose of pegaspargase every 21 days (a cycle) for a maximum of 6 cycles. dose expansion, relapsed or refractory patients (part 2):Patients with relapsed or refractor extranodal natural killer/T-cell lymphoma (nasal type) will receive liposomal mitoxantrone hydrochloride at RP2D plus a standard dose of pegaspargase every 21 days (a cycle) for a maximum of 6 cycles.

Drug: Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase; Drug: Part 2 (treatment-naïve patients): Liposomal mitoxantrone hydrochloride and Pegaspargase; Drug: Part 2 (relapsed or refractory patients): Liposomal mitoxantrone hydrochloride and Pegaspargase

Interventions

Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase DRUG

Drug: Liposomal mitoxantrone hydrochloride (12mg/m2, 16mg/m2, 20mg/m2, 24mg/m2) is administered by an intravenous infusion (IV) on day 1 of each 21-day cycle. Drug: Pegaspargase (2000IU/m2) is administered by an intramuscular injection (IM) on day 1 of each 21-day cycle.

Also known as: Part 1

dose escalation (part 1)

Part 2 (treatment-naïve patients): Liposomal mitoxantrone hydrochloride and Pegaspargase DRUG

Drug: Liposomal mitoxantrone hydrochloride (RP2D defined in Part 1) is administered by an intravenous infusion (IV) on day 1 of each 21-day cycle. Drug: Pegaspargase (2000IU/m2) is administered by an intramuscular injection (IM) on day 1 of each 21-day cycle.

Also known as: Part 2 (treatment-naïve patients)

dose escalation (part 1)

Part 2 (relapsed or refractory patients): Liposomal mitoxantrone hydrochloride and Pegaspargase DRUG

Drug: Liposomal mitoxantrone hydrochloride (RP2D defined in Part 1) is administered by an intravenous infusion (IV) on day 1 of each 21-day cycle. Drug: Pegaspargase (2000IU/m2) is administered by an intramuscular injection (IM) on day 1 of each 21-day cycle.

Also known as: Part 2 (relapsed or refractory patients)

dose escalation (part 1)

Eligibility Criteria

• Age: 18 Years - 75 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, ≤75 years, no gender limitation;
• Histologically confirmed diagnosis of treatment-naïve, relapsed or refractory extranodal NK/T-cell lymphoma nasal type (NKTCL);
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• At least one measurable lesion as per Lugano 2014 criteria;
• Adequate bone marrow, liver, renal and coagulation function

You may not qualify if:

• Known central nervous system involvement caused by lymphoma;
• Known infiltration of the bone marrow according to criteria for leukemia (≥20% myeloblast in the blood or bone marrow);
• Known hemophagocytic syndrome;
• History of allergy and contraindications to mitoxantrone hydrochloride and/or asparaginase/ pegaspargase;
• Chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks of the first dose of the study drug (2 weeks for the local radiation therapy for pain relief);
• Life expectancy \< 3 months
• Impaired cardiac function or serious cardiac disease;
• Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection;
• Acute symptomatic or chronic pancreatitis within 4 weeks prior to screening;
• History of, or known additional tumor (exception: non-melanoma skin cancer (in situ) and cervical cancer (in situ) which have been cured and have not recurred within 5 years);
• History of solid organ transplantation, autologous hematopoietic stem cell transplantation within 6 months prior to screening, or allogeneic hematopoietic stem cell transplantation before screening;
• Major surgery within 4 weeks prior to screening. Or have a surgical schedule during the study period;
• A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator;
• Uncontrolled diabetes at screening;
• Known alcohol or drug abuse;

Sponsors & Collaborators

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

Study Sites (1)

the Affiliated Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, 550000, China

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell

Interventions

pegaspargase

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Ping Liu

  39 Lianhuachi East Road, Haidian Dist., Beijing, China

  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 6, 2020
• First Posted: August 12, 2020
• Study Start: September 15, 2020
• Primary Completion: January 30, 2022
• Study Completion: January 30, 2022
• Last Updated: March 7, 2024

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)