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

Primary Purpose

Extranodal NK/T-cell Lymphoma, Nasal Type

Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase
Part 2 (treatment-naïve patients): Liposomal mitoxantrone hydrochloride and Pegaspargase
Part 2 (relapsed or refractory patients): Liposomal mitoxantrone hydrochloride and Pegaspargase
Sponsored by
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extranodal NK/T-cell Lymphoma, Nasal Type

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    dose escalation (part 1)

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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
    Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)
    CR rates at the end of chemotherapy
    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)
    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)

    Secondary Outcome Measures

    Part 1 the preliminary antitumor efficacy: complete response rate (CR)
    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)
    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)
    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
    maximum concentration(Cmax)
    Part 1: The pharmacokinetic parameters AUC0-t
    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)
    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)
    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)
    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
    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
    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)

    Full Information

    First Posted
    August 6, 2020
    Last Updated
    August 9, 2020
    Sponsor
    CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04509466
    Brief Title
    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

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    August 15, 2020 (Anticipated)
    Primary Completion Date
    March 15, 2021 (Anticipated)
    Study Completion Date
    June 15, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. 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).
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Extranodal NK/T-cell Lymphoma, Nasal Type

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    104 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    dose escalation (part 1)
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Part 1: Liposomal mitoxantrone hydrochloride and Pegaspargase
    Other Intervention Name(s)
    Part 1
    Intervention Description
    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
    Intervention Name(s)
    Part 2 (treatment-naïve patients): Liposomal mitoxantrone hydrochloride and Pegaspargase
    Other Intervention Name(s)
    Part 2 (treatment-naïve patients)
    Intervention Description
    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
    Intervention Name(s)
    Part 2 (relapsed or refractory patients): Liposomal mitoxantrone hydrochloride and Pegaspargase
    Other Intervention Name(s)
    Part 2 (relapsed or refractory patients)
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Part 1:dose limiting toxicities (DLTs)
    Description
    The incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams
    Time Frame
    Cycle 1 (a cycle = 21 days)
    Title
    Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)
    Description
    CR rates at the end of chemotherapy
    Time Frame
    up to 18 weeks
    Title
    Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
    Description
    CR rates at the end of treatment(including chemotherapy and radiation)
    Time Frame
    up to 26 weeks
    Title
    Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR)
    Description
    PR rates at the end of treatment(including chemotherapy and radiation)
    Time Frame
    up to 26 weeks
    Secondary Outcome Measure Information:
    Title
    Part 1 the preliminary antitumor efficacy: complete response rate (CR)
    Description
    the percentage of patients who achieve complete response (CR)(including at the end of chemotherapy and at the end of treatment)
    Time Frame
    up to 26 weeks
    Title
    Part 1 the preliminary antitumor efficacy:overall response rate (ORR)
    Description
    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)
    Time Frame
    up to 26 weeks
    Title
    Part 1 the preliminary antitumor efficacy:disease control rate (DCR)
    Description
    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)
    Time Frame
    up to 26 weeks
    Title
    Part 1: The pharmacokinetic parameters Cmax
    Description
    maximum concentration(Cmax)
    Time Frame
    At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)
    Title
    Part 1: The pharmacokinetic parameters AUC0-t
    Description
    area under the curve from zero to the time point(AUC0-t)
    Time Frame
    At the end of Cycle 1 and Cycle 3 (each cycle is 21 days)
    Title
    Part 2 (treatment-naïve patients):The preliminary antitumor efficacy complete response rate (CR)
    Description
    the percentage of patients who achieve complete response (CR)(including at the end of chemotherapy and at the end of treatment)
    Time Frame
    up to 26 weeks
    Title
    Part 2 (treatment-naïve patients):The preliminary antitumor efficacy overall response rate (ORR)
    Description
    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)
    Time Frame
    up to 26 weeks
    Title
    Part 2 (treatment-naïve patients):The preliminary antitumor efficacy disease control rate (DCR)
    Description
    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)
    Time Frame
    up to 26 weeks
    Title
    Part 2 (treatment-naïve patients):The preliminary safety index
    Description
    The incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams
    Time Frame
    through study completion, an average of 1 year
    Title
    Part 2 (relapsed or refractory patients): The preliminary antitumor efficacy
    Description
    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)
    Time Frame
    up to 26 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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); 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; Known psychiatric disorders or cognitive disorder; 17. Pregnant or breastfeeding women, or patients who are expecting to conceive or father in 12 months (starting with the screening visit); Not suitable for this study as determined by the investigator due to other reasons.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hongmei Lin
    Phone
    15910575714
    Email
    linhongmei@mail.ecspc.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ping Liu
    Organizational Affiliation
    39 Lianhuachi East Road, Haidian Dist., Beijing, China
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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