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

NCT ID: NCT04509466

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2022-01-30

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).

Detailed Description

This is a multicentre, open-label, single-arm, phase I/II clinical study with a dose-escalation stage (part 1) and a dose-expansion stage (part 2). In part 1, patients with treatment-naïve, relapsed/refractory extranodal natural killer/T-cell lymphoma (nasal type) will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride plus a standard dose of pegaspargase every 21 days (a cycle). The dose escalation initially will follow an accelerated titration design for the first two dosing groups, then follow a classic 3+3 design. All dose-escalation decisions will be based on the safety data generated from the currently highest dose group. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined in part 1. In part 2, additional patients will be recruited into two groups,the treatment-naïve group and the relapsed or refractory group, to receive liposomal mitoxantrone hydrochloride at the RP2D combined with a standard dose of pegaspargase. All patients will receive the treatment until disease progression, or observation of unacceptable grade 3 drug-related adverse events (a maximum of 6 cycles).

Conditions

Extranodal NK/T-cell Lymphoma, Nasal Type

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dose escalation (part 1)

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.

Group Type: EXPERIMENTAL

Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase

Intervention Type: 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.

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

Intervention Type: 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.

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

Intervention Type: 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.

Interventions

Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase

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.

Intervention Type: DRUG

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

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.

Intervention Type: DRUG

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

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.

Intervention Type: DRUG

Other Intervention Names

Part 1; Part 2 (treatment-naïve patients); Part 2 (relapsed or refractory patients)

Eligibility Criteria

Inclusion Criteria

1. Subjects fully understand and voluntarily participate in this study and sign informed consent;

2. Age ≥18, ≤75 years, no gender limitation;

3. Histologically confirmed diagnosis of treatment-naïve, relapsed or refractory extranodal NK/T-cell lymphoma nasal type (NKTCL);

4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

5. At least one measurable lesion as per Lugano 2014 criteria;

6. Adequate bone marrow, liver, renal and coagulation function

Exclusion Criteria

1. Known central nervous system involvement caused by lymphoma;

2. Known infiltration of the bone marrow according to criteria for leukemia (≥20% myeloblast in the blood or bone marrow);

3. Known hemophagocytic syndrome;

4. History of allergy and contraindications to mitoxantrone hydrochloride and/or asparaginase/ pegaspargase;

5. 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);

6. Life expectancy < 3 months

7. Impaired cardiac function or serious cardiac disease;

8. Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection;

9. Acute symptomatic or chronic pancreatitis within 4 weeks prior to screening;

10. 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);

11. History of solid organ transplantation, autologous hematopoietic stem cell transplantation within 6 months prior to screening, or allogeneic hematopoietic stem cell transplantation before screening;

12. Major surgery within 4 weeks prior to screening. Or have a surgical schedule during the study period;

13. A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator;

14. Uncontrolled diabetes at screening;

15. Known alcohol or drug abuse;

16. Known psychiatric disorders or cognitive disorder;

17. 17. Pregnant or breastfeeding women, or patients who are expecting to conceive or father in 12 months (starting with the screening visit)；

18. Not suitable for this study as determined by the investigator due to other reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ping Liu

Role: PRINCIPAL_INVESTIGATOR

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

Locations

the Affiliated Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Countries

China

Other Identifiers

HE071-CSP-012

Identifier Type: -

Identifier Source: org_study_id