Clinical Study of Liposomal Mitoxantrone Hydrochloride Injection Combined With Pegaspargase in the Treatment of NKTCL
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
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).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 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. |
Drug: 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.
Other Names:
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.
Other Names:
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Part 1:dose limiting toxicities (DLTs) [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 (treatment-naïve patients):The percentage of patients who achieve complete response (CR) [up to 18 weeks]
CR rates at the end of chemotherapy
- Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR) [up to 26 weeks]
CR rates at the end of treatment(including chemotherapy and radiation)
- Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR) [up to 26 weeks]
PR rates at the end of treatment(including chemotherapy and radiation)
Secondary Outcome Measures
- Part 1 the preliminary antitumor efficacy: complete response rate (CR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)(including at the end of chemotherapy and at the end of treatment)
- Part 1 the preliminary antitumor efficacy:overall response rate (ORR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)and partial response (PR)(including at the end of chemotherapy and at the end of treatment)
- Part 1 the preliminary antitumor efficacy:disease control rate (DCR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)、partial response (PR) and stable disease(SD)(including at the end of chemotherapy and at the end of treatment)
- Part 1: The pharmacokinetic parameters Cmax [At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)]
maximum concentration(Cmax)
- Part 1: The pharmacokinetic parameters AUC0-t [At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)]
area under the curve from zero to the time point(AUC0-t)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy complete response rate (CR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)(including at the end of chemotherapy and at the end of treatment)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy overall response rate (ORR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)and partial response (PR)(including at the end of chemotherapy and at the end of treatment)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy disease control rate (DCR) [up to 26 weeks]
the percentage of patients who achieve complete response (CR)、partial response (PR) and stable disease(SD)(including at the end of chemotherapy and at the end of treatment)
- Part 2 (treatment-naïve patients):The preliminary safety index [through study completion, an average of 1 year]
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 preliminary antitumor efficacy [up to 26 weeks]
disease control rate (DCR):the percentage of patients who achieve complete response (CR)、partial response (PR) and stable disease(SD)(including at the end of chemotherapy and at the end of treatment)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects fully understand and voluntarily participate in this study and sign informed consent;
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Age ≥18, ≤75 years, no gender limitation;
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Histologically confirmed diagnosis of treatment-naïve, relapsed or refractory extranodal NK/T-cell lymphoma nasal type (NKTCL);
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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
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At least one measurable lesion as per Lugano 2014 criteria;
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Adequate bone marrow, liver, renal and coagulation function
Exclusion Criteria:
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Known central nervous system involvement caused by lymphoma;
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Known infiltration of the bone marrow according to criteria for leukemia (≥20% myeloblast in the blood or bone marrow);
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Known hemophagocytic syndrome;
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History of allergy and contraindications to mitoxantrone hydrochloride and/or asparaginase/ pegaspargase;
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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);
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Life expectancy < 3 months
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Impaired cardiac function or serious cardiac disease;
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Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection;
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Acute symptomatic or chronic pancreatitis within 4 weeks prior to screening;
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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);
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History of solid organ transplantation, autologous hematopoietic stem cell transplantation within 6 months prior to screening, or allogeneic hematopoietic stem cell transplantation before screening;
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Major surgery within 4 weeks prior to screening. Or have a surgical schedule during the study period;
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A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator;
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Uncontrolled diabetes at screening;
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Known alcohol or drug abuse;
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Known psychiatric disorders or cognitive disorder;
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- Pregnant or breastfeeding women, or patients who are expecting to conceive or father in 12 months (starting with the screening visit);
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Not suitable for this study as determined by the investigator due to other reasons.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Investigators
- Principal Investigator: Ping Liu, 39 Lianhuachi East Road, Haidian Dist., Beijing, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HE071-CSP-012