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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

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:

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.

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

NCT ID

NCT04509466

First Posted

August 6, 2020

Last Updated

August 9, 2020

Sponsor

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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

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

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

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

Learn more about this trial

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

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