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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Extranodal NK/T-cell Lymphoma, Nasal Type
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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);
Outcomes
Primary Outcomes
Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
Time Frame: up to 26 weeks
CR rates at the end of treatment(including chemotherapy and radiation)
Part 1：dose limiting toxicities (DLTs)
Time Frame: Cycle 1 (a cycle = 21 days)
The incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams
Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR)
Time Frame: up to 26 weeks
PR rates at the end of treatment(including chemotherapy and radiation)
Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)
Time Frame: up to 18 weeks
CR rates at the end of chemotherapy
Secondary Outcomes
- 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 AUC0-t(At the end of Cycle 1 and Cycle 3 (each cycle is 21 days))
- Part 2 (relapsed or refractory patients): The preliminary antitumor efficacy(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 2 (treatment-naïve patients):The preliminary antitumor efficacy overall response rate (ORR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary safety index(through study completion, an average of 1 year)
- Part 1 the preliminary antitumor efficacy: complete response rate (CR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy complete response rate (CR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy disease control rate (DCR)(up to 26 weeks)