Clinical trial NCT04509466: Clinical Study of Liposomal Mitoxantrone Hydrochloride Injection Combined With Pegaspargase in the Treatment of NKTCL
Official title: A Multicentre, Open-label, Single-arm, Phase I/II Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Liposomal Mitoxantrone Hydrochloride Injection Combined With Pegaspargase in the Treatment of NKTCL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Extranodal NK/T-cell Lymphoma, Nasal Type
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-08-12
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Part 1：dose limiting toxicities (DLTs)
timeFrame: Cycle 1 (a cycle = 21 days)
measure: Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)
timeFrame: up to 18 weeks
measure: Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
timeFrame: up to 26 weeks
measure: Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR)
timeFrame: up to 26 weeks
Secondary outcomes:
measure: Part 1 the preliminary antitumor efficacy: complete response rate (CR)
timeFrame: up to 26 weeks
measure: Part 1 the preliminary antitumor efficacy：overall response rate (ORR)
timeFrame: up to 26 weeks
measure: Part 1 the preliminary antitumor efficacy:disease control rate (DCR)
timeFrame: up to 26 weeks
measure: Part 1: The pharmacokinetic parameters Cmax
timeFrame: At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: Part 1: The pharmacokinetic parameters AUC0-t
timeFrame: At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: Part 2 (treatment-naïve patients):The preliminary antitumor efficacy complete response rate (CR)
timeFrame: up to 26 weeks
measure: Part 2 (treatment-naïve patients):The preliminary antitumor efficacy overall response rate (ORR)
timeFrame: up to 26 weeks
measure: Part 2 (treatment-naïve patients):The preliminary antitumor efficacy disease control rate (DCR)
timeFrame: up to 26 weeks
measure: Part 2 (treatment-naïve patients):The preliminary safety index
timeFrame: through study completion, an average of 1 year
measure: Part 2 (relapsed or refractory patients): The preliminary antitumor efficacy
timeFrame: up to 26 weeks
Other outcomes:
Locations:
city: Guiyang
country: China
facility: the Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
Study officials:
affiliation: 39 Lianhuachi East Road, Haidian Dist., Beijing, China
name: Ping Liu
role: PRINCIPAL_INVESTIGATOR
References: