<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03776279</url>
  </required_header>
  <id_info>
    <org_study_id>PLM60-PTCL</org_study_id>
    <nct_id>NCT03776279</nct_id>
  </id_info>
  <brief_title>A Study of Liposome-entrapped Mitoxantrone Hydrochloride Injection in Relapsed/Refractory Peripheral T-cell Lymphoma and NK/T-cell Lymphoma</brief_title>
  <official_title>Single-arm, Open and Multi-center Phase II Study of Liposome-entrapped Mitoxantrone Hydrochloride Injection in Relapsed/Refractory Peripheral T-cell Lymphoma and NK/T-cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CSPC ZhongQi Pharmaceutical Technology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CSPC ZhongQi Pharmaceutical Technology Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm, open, multi-center, phase II study to evaluate the efficacy and safety&#xD;
      of Mitoxantrone Hydrochloride Liposome Injection in Relapsed or refractory peripheral t-cell&#xD;
      and NK/T-cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The dosage regimen of Liposome-entrapped Mitoxantrone is multi-cycle 20mg/m2 intravenous&#xD;
      infusion. Every 4 weeks is a treatment cycle, with administration on the first day of each&#xD;
      cycle. End-of-treatment visit will be made to the subjects within 4 weeks after the end of&#xD;
      the last administration. Progression-free survival (PFS) follow-up will be conducted to the&#xD;
      subjects in stable or improved condition after treatment and the subjects with early&#xD;
      termination of treatment due to intolerance in Week 8 after the last administration of study&#xD;
      drug, and thereafter once every 8 weeks until PD, death, withdrawal of informed consent form&#xD;
      (ICF), starting another new treatment or end of the entire study (whichever occurs first).&#xD;
      Meanwhile, overall survival (OS) follow-up will also be conducted to the subjects with PD and&#xD;
      starting another new treatment once every 8 weeks until death, withdrawal of ICF or end of&#xD;
      the entire study (whichever occurs first).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 2, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>&gt;4weeks</time_frame>
    <description>The percentage of complete response (CR) and partial response (PR) in all the enrolled subjects from the date of the first administration (calculated by the optimum response during the entire study period)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response(DoR)</measure>
    <time_frame>&gt;3 months</time_frame>
    <description>The duration from achieving effective treatment (CR or PR recorded for the first time) until definite relapse or progression for the first time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival(PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>The duration from the first administration date until lymphoma progression (PD evaluated by imaging diagnosis) date or all-cause death date (whichever occurs first).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>3 years</time_frame>
    <description>The duration from the first administration date until all-cause death date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate(DCR)</measure>
    <time_frame>3 years</time_frame>
    <description>The percentage of CR and PR in all the enrolled subjects from the date of the first administration, including the subjects with CR, PRC or SD</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">106</enrollment>
  <condition>Relapsed or Refractory Peripheral T-cell and NK/T-cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Mitoxantrone Hydrochloride Liposome Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks is a treatment cycle, and the first day of each cycle is administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitoxantrone Hydrochloride Liposome Injection</intervention_name>
    <description>Mitoxantrone Hydrochloride Liposome Injection 20 mg/m2 will be infused intravenously once over 60min in 250 ml 5％ glucose injection on the first day during a treatment phase of 4 weeks.</description>
    <arm_group_label>Mitoxantrone Hydrochloride Liposome Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
        Subjects must satisfy all the following conditions before enrollment:&#xD;
&#xD;
          1. Those who have fully understood the study and have signed the ICF.&#xD;
&#xD;
          2. Male or female, aged 18 or above (including 18).&#xD;
&#xD;
          3. Those with PTCL and NK/T-cell lymphoma confirmed by histopathological and/or&#xD;
             cytological examination, with the subtypes as follows:&#xD;
&#xD;
               1. Peripheral T-cell lymphoma, unspecified (PTCL, NOS)&#xD;
&#xD;
               2. Angioimmunoblastic T-cell lymphoma (AITL)&#xD;
&#xD;
               3. ALK+systematic anaplastic large T-cell lymphoma (ALCL, ALK+)&#xD;
&#xD;
               4. ALK-systematic anaplastic large T-cell lymphoma (ALCL，ALK-)&#xD;
&#xD;
               5. Extranobal NK/T cell lymphoma (nasal type) (NKTCL)&#xD;
&#xD;
               6. Enteropathy-associated T-cell lymphoma (EATCL, Type I (traditional type), Type&#xD;
                  II)&#xD;
&#xD;
               7. Hepatosplenic γδ T-cell lymphoma (HSTCL, γδT) hOther non-Hodgkin's lymphomas from&#xD;
                  invasive T-cells (other than highly invasive cells) approved by the sponsor, who&#xD;
                  may be enrolled in the opinion of the investigator.&#xD;
&#xD;
          4. Those receivd at least first-line standard treatment (including chemotherapy and&#xD;
             autologous hematopoietic stem cell transplantation) If anthracycline or&#xD;
             anthracycline-containing chemotherapy has been used in the past, the efficacy is&#xD;
             assessed as response; if they were NK/T-cell lymphoma patients, they need to be&#xD;
             treated with asparaginase (or pepsinase, L-asparaginase) treatment.&#xD;
&#xD;
          5. Subjects who must provide the written pathological/histological diagnosis report&#xD;
             during the screening period, and agree to provide the tumor tissue sections or fresh&#xD;
             tumor tissues to the Center Laboratory for testing.&#xD;
&#xD;
          6. Those with ECOG performance status score of 0 or 1.&#xD;
&#xD;
          7. The estimated survival time was at least 12 weeks.&#xD;
&#xD;
          8. Those at least with one measurable lesion in accordance with the revised standard for&#xD;
             evaluation of efficacy in malignant lymphoma (Version 2007): the long axis of the&#xD;
             lesion shall be&gt;1.5 cm or 1.0~1.5 cm and the short axis of the lesion shall be&gt;1.0 cm.&#xD;
&#xD;
          9. Subjects who shall meet the following requirements for laboratory examination when&#xD;
             screening and who have not received cell growth factor (long-acting granulocyte-colony&#xD;
             stimulating factor [G-CSF] and [PEG-CSF] shall have the interval of 14 days) and&#xD;
             platelet or granulocyte infusion within 7 days before hematological evaluation for&#xD;
             screening:&#xD;
&#xD;
               1. Absolute value of neutrophils ≥ 1.5 × 109/ L in subjects without involvement of&#xD;
                  bone marrow; absolute value of neutrophil ≥ 1.0 × 109/ L in subjects with&#xD;
                  involvement of bone marrow;&#xD;
&#xD;
               2. Hemoglobin ≥ 90 g/L (without red cell infusion within 14 days), hemoglobin ≥ 75&#xD;
                  g/ L in subjects with involvement of bone marrow;&#xD;
&#xD;
               3. Platelet ≥ 75 × 109/ L in subjects without involvement of bone marrow; platelet ≥&#xD;
                  50 × 109/ L in subjects with involvement of bone marrow;&#xD;
&#xD;
               4. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) (total bilirubin ≤ 3 ×&#xD;
                  ULN if bilirubin level increase is caused by lymphoma invading the liver);&#xD;
&#xD;
               5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN; if&#xD;
                  AST or ALT increase is caused by lymphoma invading the liver, both AST and ALT&#xD;
                  shall be ≤ 5 × ULN);&#xD;
&#xD;
               6. Creatinine &lt; 1.5 × ULN.&#xD;
&#xD;
         10. Female subjects:&#xD;
&#xD;
               1. Without fertility (i.e., unable to get pregnant under physiological condition),&#xD;
                  including postmenopausal (complete cessation of menstruation for ≥ 1 year) or&#xD;
                  documented irreversible sterilization including hysterectomy, bilateral&#xD;
                  ovariectomy or bilateral salpingectomy (rather than tubal ligation);&#xD;
&#xD;
               2. With fertility potential, who shall be negative when serum pregnancy test&#xD;
                  screening (within 7 days of the first administration of study drug) and agree to&#xD;
                  take effective contraception measures during the study period and within 90 days&#xD;
                  after the last administration. Subjects shall always practice contraception&#xD;
                  strictly in accordance with the labels of contraceptive drugs/devices and the&#xD;
                  instructions of the investigator. Effective contraception measures shall be&#xD;
                  defined as follows:&#xD;
&#xD;
             i)Sex partner vasectomized is the sole sex partner of the female subject; ii)Use of&#xD;
             IUDs with a failure rate of less than 1% per year iii)Double contraception, e.g.&#xD;
             spermatocide plus male condom, female condom, diaphragm, cervical cap or intrauterine&#xD;
             device.&#xD;
&#xD;
             Male subjects: who shall have received the vasectomy, or agree to take effective&#xD;
             contraception measures during the study period and within 30 days after the last&#xD;
             administration.&#xD;
&#xD;
         11. Subjects who are able to comply with the study procedures, restrictions and&#xD;
             requirements as judged by the investigator.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        Subjects consistent with any one of the following conditions:&#xD;
&#xD;
          1. Subjects in lymphoma leukemia (malignant cell proportion of &gt; 20% in bone marrow&#xD;
             examination);&#xD;
&#xD;
          2. Subjects are consistent with one of the following conditions in the previous&#xD;
             anti-tumor treatment history:&#xD;
&#xD;
               1. Those receiving Mitoxantrone or Liposome-entrapped Mitoxantrone previously;&#xD;
&#xD;
               2. Those receiving treatment of Adriamycin or other anthracyclines previously, with&#xD;
                  the total cumulative dose of &gt; 360 mg/m2 (when converted to 1 mg Adriamycin,&#xD;
                  other anthracyclines shall be equivalent to 2 mg Epirubicin or 2 mg Pirarubicin&#xD;
                  or 2 mg Daunorubicin or 0.5 mg Idarubicin);&#xD;
&#xD;
               3. Those receiving anti-tumor treatment (including chemotherapy, radiotherapy,&#xD;
                  hormone therapy or administration of TCM with anti-tumor activity) within 4 weeks&#xD;
                  prior to the first use of the study drug);&#xD;
&#xD;
               4. Those receiving autologous hematopoietic stem cell transplantation within 6&#xD;
                  months;&#xD;
&#xD;
               5. Those receiving allogeneic hematopoietic stem cell transplantation previously.&#xD;
&#xD;
          3. Those receiving major surgery (the definition of major surgery shall refer to the&#xD;
             Level 3 or 4 surgery stipulated in the Management Practices of Clinical Application of&#xD;
             Medical Technology) within 4 weeks prior to enrollment or those who have not&#xD;
             completely recovered from any previous invasive operation.&#xD;
&#xD;
          4. Those who have not recovered from toxic response in the previous anti-tumor treatment&#xD;
             (&gt;Grade 1 in NCI-CTCAE [Version 4.03], with the exception of hair loss and&#xD;
             pigmentation.&#xD;
&#xD;
          5. Those with other malignant tumors previously or currently (except the non-melanoma&#xD;
             skin basal cell carcinoma under effective control, breast/cervical carcinoma in situ,&#xD;
             and other malignant tumors not treated but under effective control in the past five&#xD;
             years).&#xD;
&#xD;
          6. Subjects with known or existing primary or metastatic central nervous system lymphoma,&#xD;
             or with existing other cerebral/meningeal diseases.&#xD;
&#xD;
          7. Subjects with uncontrolled hypertension (refers to systolic pressure of 180 mmHg&#xD;
             and/or diastolic pressure of 100 mmHg after treatment).&#xD;
&#xD;
          8. Subjects with active hemorrhagic disease.&#xD;
&#xD;
          9. Subjects with active infection, including hepatitis B (positive hepatitis B virus&#xD;
             surface antigen and hepatitis B virus DNA of more than 1,000 copies/mL) and hepatitis&#xD;
             C (positive hepatitis C virus RNA).&#xD;
&#xD;
         10. Human immunodeficiency virus (HIV) infection (HIV positive).&#xD;
&#xD;
         11. Subjects with history of hepatic fibrosis or cirrhosis or with clinical signs and&#xD;
             symptoms suggestive of liver fibrosis or cirrhosis.&#xD;
&#xD;
         12. Subjects with the cardiac function and disease:&#xD;
&#xD;
               1. Male: QTc&gt;450 ms, female: QTc&gt;470 ms when ECG examination in the Research Center&#xD;
                  during the screening period;&#xD;
&#xD;
               2. Clinically significant arrhythmias, including but not limited to complete left&#xD;
                  bundle branch block, Degree II atrioventricular block and PR interval &gt; 250 ms;&#xD;
&#xD;
               3. Any risk factor that might increase the QTc interval, e.g. hypokalaemia,&#xD;
                  inherited long-QT syndrome, with current administration of the drug for&#xD;
                  prolonging the QT interval or discontinuance for less than 15 days;&#xD;
&#xD;
               4. Congestive heart failure of ≥Grade 2 in the New York Heart Association;&#xD;
&#xD;
               5. Cardiac ejection fraction less than 50% or less than the lower limit of&#xD;
                  laboratory examination vale range of Research Center;&#xD;
&#xD;
               6. Within six months prior to recruitment occurred myocardial infarction, unstable&#xD;
                  angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring&#xD;
                  treatment, clinical history of severe pericardial disease, or&#xD;
                  electrocardiographic evidence of acute ischemia or abnormal active conduction&#xD;
                  system.&#xD;
&#xD;
         13. Subjects with known history of immediate or delayed hypersensitivity to the similar&#xD;
             drug and excipient of the study drug.&#xD;
&#xD;
         14. Pregnant or lactating women.&#xD;
&#xD;
         15. According to the judgement of the investigators ,Those with any severe or uncontrolled&#xD;
             systematic disease, systematic complication, other severe complicated diseases (e.g.&#xD;
             hemophagocytic syndrome) or special tumor condition that might make the subjects&#xD;
             unsuitable for entry into the study or might affect the compliance to the protocol or&#xD;
             might cause significant interference with the correct evaluation of safety, toxicity&#xD;
             and efficacy of the study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Huiqiang Huang, Doctor</last_name>
    <phone>020-87343350</phone>
    <email>huanghq@sysucc.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Huiqiang Huang, Doctor</last_name>
      <phone>020-87343350</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>December 13, 2018</last_update_submitted>
  <last_update_submitted_qc>December 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitoxantrone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03776279
org study id: PLM60-PTCL
nct id: NCT03776279
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single-arm, open, multi-center, phase II study to evaluate the efficacy and safety
      of Mitoxantrone Hydrochloride Liposome Injection in Relapsed or refractory peripheral t-cell
      and NK/T-cell lymphoma.
The dosage regimen of Liposome-entrapped Mitoxantrone is multi-cycle 20mg/m2 intravenous
      infusion. Every 4 weeks is a treatment cycle, with administration on the first day of each
      cycle. End-of-treatment visit will be made to the subjects within 4 weeks after the end of
      the last administration. Progression-free survival (PFS) follow-up will be conducted to the
      subjects in stable or improved condition after treatment and the subjects with early
      termination of treatment due to intolerance in Week 8 after the last administration of study
      drug, and thereafter once every 8 weeks until PD, death, withdrawal of informed consent form
      (ICF), starting another new treatment or end of the entire study (whichever occurs first).
      Meanwhile, overall survival (OS) follow-up will also be conducted to the subjects with PD and
      starting another new treatment once every 8 weeks until death, withdrawal of ICF or end of
      the entire study (whichever occurs first).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: >4weeks
description: The percentage of complete response (CR) and partial response (PR) in all the enrolled subjects from the date of the first administration (calculated by the optimum response during the entire study period)
measure: Duration of Response(DoR)
time frame: >3 months
description: The duration from achieving effective treatment (CR or PR recorded for the first time) until definite relapse or progression for the first time.
measure: Progression-free survival(PFS)
time frame: 3 years
description: The duration from the first administration date until lymphoma progression (PD evaluated by imaging diagnosis) date or all-cause death date (whichever occurs first).
measure: Overall survival(OS)
time frame: 3 years
description: The duration from the first administration date until all-cause death date.
measure: Disease control rate(DCR)
time frame: 3 years
description: The percentage of CR and PR in all the enrolled subjects from the date of the first administration, including the subjects with CR, PRC or SD
arm group label: Mitoxantrone Hydrochloride Liposome Injection
arm group type: Experimental
description: 4 weeks is a treatment cycle, and the first day of each cycle is administered.
intervention type: Drug
intervention name: Mitoxantrone Hydrochloride Liposome Injection
description: Mitoxantrone Hydrochloride Liposome Injection 20 mg/m2 will be infused intravenously once over 60min in 250 ml 5％ glucose injection on the first day during a treatment phase of 4 weeks.
arm group label: Mitoxantrone Hydrochloride Liposome Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Huiqiang Huang, Doctor
phone: 020-87343350
email: huanghq@sysucc.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Mitoxantrone