<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/NCT03836768</url>
  </required_header>
  <id_info>
    <org_study_id>DTRM_DTRMWXHS-12_004</org_study_id>
    <nct_id>NCT03836768</nct_id>
  </id_info>
  <brief_title>BTK Inhibitor DTRMWXHS-12 in Mantle Cell Lymphoma</brief_title>
  <official_title>A Phase Ib Study of BTK Inhibitor DTRMWXHS-12 in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang DTRM Biopharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhejiang DTRM Biopharma</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Primary Objective is to evaluate the safety and tolerability of the DTRMWXHS-12 capsule&#xD;
      in patients with relapsed/refractory MCL and recommend the dose and dosing method (RP2D) used&#xD;
      in phase II study.&#xD;
&#xD;
      The Secondary Objective is to evaluate the pharmacokinetics (PK) of multiple dose oral&#xD;
      administration of DTRMWXHS-12 capsule in patients with relapsed/refractory MCL.&#xD;
&#xD;
      The Exploratory Objective is to preliminarily evaluate the efficacy of DTRMWXHS-12 capsule in&#xD;
      patients with relapsed/refractory MCL.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2019</start_date>
  <completion_date type="Actual">November 17, 2021</completion_date>
  <primary_completion_date type="Actual">November 17, 2021</primary_completion_date>
  <phase>Phase 1</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>Safety: Incidence and severity of (serious) adverse events n each patient according to the NCI-CTCAE4.03 grading</measure>
    <time_frame>Starting from date of first dose up to 35 days after last dose</time_frame>
    <description>To monitor AEs and SAEs in each patient according to the NCI-CTCAE4.03 grading criteria by evaluating changes in physical examination, laboratory tests, and 12-lead ECG during the whole study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>concentration of drug in plasma</measure>
    <time_frame>From date of first dose to day 56</time_frame>
    <description>concentration of drug in plasma</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>From date of first dose to date of disease progression, an average of 6 months</time_frame>
    <description>Percentage of patients with PR, CR</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Experimental Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DTRMWXHS-12, oral capsule, daily, 28 days as a cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DTRMWXHS-12</intervention_name>
    <description>DTRMWXHS-12 capsules: 150 mg, 300 mg</description>
    <arm_group_label>Experimental Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. 18-75 Years old (include 18 and 75), gender is not limited.&#xD;
&#xD;
          2. Measurable lesions by computed tomography (CT)/magnetic resonance imaging (MRI). A&#xD;
             measurable lesion is defined as follows: at least the longest diameter of one lymph&#xD;
             node &gt;1.5cm and clearly measurable in two vertical directions, or at least the longest&#xD;
             diameter of one extranodal lesion &gt;1cm (e.g., liver nodule); If only spleen or&#xD;
             gastrointestinal mucosa is involved, corresponding examinations and evaluations will&#xD;
             be conducted in the investigator's opinion.&#xD;
&#xD;
          3. The diagnosis report must contain morphology and evidence of positive cyclin D1 by&#xD;
             immunohistochemistry or evidence of t (11; 14). The above results are tested by&#xD;
             immunohistochemistry, cytogenetics or Fluorescent in situ hybridization (FISH). After&#xD;
             enrollment, tumor tissue (FFPE) blocks or sections must be sent to the central&#xD;
             laboratory for confirmation of MCL.&#xD;
&#xD;
          4. The laboratory parameters are as follows:&#xD;
&#xD;
               1. Hematology: Neutrophils ≥ 1.0×10^9/L without growth factor or blood transfusion,&#xD;
                  platelets ≥ 75×10^9L (≥50×10^9/L if bone marrow is involved), and hemoglobins &gt;&#xD;
                  9g/dL within 7 days before enrollment into the study.&#xD;
&#xD;
               2. Liver: Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase&#xD;
                  (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase&#xD;
                  (SGPT) ≤ 2.5×ULN; total bilirubin ≤ 2×ULN (&lt; 3×ULN when diagnosed as Gilbert's&#xD;
                  syndrome).&#xD;
&#xD;
               3. Kidney: Creatinine clearance≥30 ml/min (Evaluated by estimated glomerular&#xD;
                  filtration rate [eGFR] according to the Cockcroft-Gault Equation or the&#xD;
                  calculation equation of each site); Cockcroft-Gault equation= Female:&#xD;
                  (140-age)×weight(kg)×0.85/(72×serum creatinine (mg/dL)) Male: (140-age)×body&#xD;
                  weight(kg)/(72×serum creatinine(mg/dL))&#xD;
&#xD;
               4. international normalized ratio(INR) ≤ 1.5×ULN and activated partial&#xD;
                  thromboplastin time (APTT) ≤ 1.5×ULN, and for patients with acquired hemophilia&#xD;
                  or those treated with clotting factor inhibitors or vitamin K antagonists, the&#xD;
                  enrollment will be determined after discussion with the investigator.&#xD;
&#xD;
          5. ECOG performance status score 0-2.&#xD;
&#xD;
          6. Life expectancy &gt; 3 months.&#xD;
&#xD;
          7. There must be documentations on relapsed or refractory lymphoma or disease progression&#xD;
             after systemic therapy and at least one but less than five therapies for mantle cell&#xD;
             lymphoma were administrated previously (1 ≤ number of previous therapies &lt; 5).&#xD;
&#xD;
          8. No response with the last therapy (SD or PD during the treatment), or PD after the&#xD;
             therapy.&#xD;
&#xD;
          9. Patients with disease recurrence at least 3 months after autologous hematopoietic stem&#xD;
             cell transplantation can be enrolled into the study, if there isn't any relevant&#xD;
             active infection.&#xD;
&#xD;
         10. Females of child-bearing potential must agree to use highly effective contraception&#xD;
             methods during the study and at least 180 days after the last dose of the&#xD;
             investigational drug. Highly effective contraception methods include abstinence,&#xD;
             hysterectomy, bilateral ovariectomy without menstruation for six consecutive months,&#xD;
             intrauterine contraception systems, hormonal contraception such as injectable&#xD;
             contraceptives and oral contraceptives. Males must be sterilized via either vasectomy,&#xD;
             or use barrier methods, while their female partners should take the effective&#xD;
             contraception methods mentioned above.&#xD;
&#xD;
         11. Patients are voluntary to sign the informed consent form and can understand and comply&#xD;
             with all study requirements.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Patients suffering from or previously suffering from CNS lymphoma.&#xD;
&#xD;
          2. Patients received other BTK inhibitors prior to enrollment. Patients who received&#xD;
             steroid anti-tumor therapy (a dose equivalent to&gt;20mg/day of prednisone) within 7&#xD;
             days, or received chemotherapy, targeted therapy, or radiotherapy within 4 weeks, or&#xD;
             received anti-tumor Chinese medicinal herbs or antibody therapy within 4 weeks, prior&#xD;
             to first administration of DTRMWXHS-12 capsule.&#xD;
&#xD;
          3. Patients received major surgery in the past 4 weeks before screening (determined by&#xD;
             the investigator according to the patient's condition).&#xD;
&#xD;
          4. Patients with active bleeding or combination with anticoagulant therapy within 3-6&#xD;
             months.&#xD;
&#xD;
          5. Patients had undergone chemotherapy before and in whom the toxicity has not resolved&#xD;
             (the toxicity has not resolved to ≤ grade 1 as per National Cancer Institute's Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) Version 4.03, except for hair loss,&#xD;
             absolute neutrophil count (ANC) and platelets). For neutrophils and platelets, please&#xD;
             refer to the criterion 4 [Neutrophils] and [Platelets] in the inclusion criteria.&#xD;
&#xD;
          6. Patients with a history of other active malignant diseases within 2 years prior to&#xD;
             enrollment into the study, excluding the following: (1) adequately treated cervical&#xD;
             carcinoma in situ; (2) local skin basal cell carcinoma or squamous cell carcinoma; (3)&#xD;
             malignant diseases that has been controlled and completely locally treated (by surgery&#xD;
             or other means)&#xD;
&#xD;
          7. Patients suffering from active cardiovascular diseases with clinical significance,&#xD;
             such as uncontrolled arrhythmia, congestive heart failure, Grade 3 or 4 heart disease&#xD;
             according to New York Heart Association (NYHA) Functional Classification, or those&#xD;
             with history of myocardial infarction within 6 months before screening.&#xD;
&#xD;
          8. QTcF&gt;450 msecs or other significant ECG abnormalities, including second-degree&#xD;
             atrioventricular block type Ⅱ, third-degree atrioventricular block.&#xD;
&#xD;
          9. Patients who can't swallow capsules or with diseases significantly affect the&#xD;
             gastrointestinal function, such as malabsorption syndrome, gastric or intestinal&#xD;
             resection, symptomatic inflammatory bowel disease, or partial or complete intestinal&#xD;
             obstruction.&#xD;
&#xD;
         10. Uncontrolled systemic infections or infections requiring to be treated with&#xD;
             intravenous antibacterial agents.&#xD;
&#xD;
         11. Patients who previously received allogeneic stem cell transplantation.&#xD;
&#xD;
         12. Patients known to have been infected with human immunodeficiency virus (HIV) or active&#xD;
             hepatitis B or hepatitis C virus (polymerase chain reaction [PCR] or reverse&#xD;
             transcription- polymerase chain reaction (RT-PCR) shows positive results).&#xD;
&#xD;
         13. Hepatitis B test includes HBsAg, HBcAb and HBsAb. If the patient is HBsAg-negative but&#xD;
             HBcAb-positive (regardless of HBsAb), the PCR technology will be used to detect&#xD;
             hepatitis B virus (HBV) DNA, and the acceptable upper limit of normal in the table&#xD;
             below is 1000 IU/mL. Considering different PCR kits may be used by different sites,&#xD;
             the acceptable upper limit of normal for HBV DNA should be the normal value in the&#xD;
             site. Hepatitis C test includes hepatitis C virus (HCV) antibody test, and if the HCV&#xD;
             antibody is positive, the RT-PCR technology will be used to detect HCV RNA.&#xD;
&#xD;
         14. Pregnant or lactating women.&#xD;
&#xD;
         15. Any life-threatening disease, medical condition, or organ system dysfunction that, in&#xD;
             the investigator's opinion, may affect subject safety or lead to study risks.&#xD;
&#xD;
         16. Patients with poor compliance.&#xD;
&#xD;
         17. Patients who receive treatment with a potent CYP3A (cytochrome P450, family 3,&#xD;
             subfamily A) inhibitor or a potent CYP3A inducer within 7 days prior to enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei He, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Zhejiang DTRM Biopharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</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, Mantle-Cell</mesh_term>
  </condition_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/NCT03836768
org study id: DTRM_DTRMWXHS-12_004
nct id: NCT03836768
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The Primary Objective is to evaluate the safety and tolerability of the DTRMWXHS-12 capsule
      in patients with relapsed/refractory MCL and recommend the dose and dosing method (RP2D) used
      in phase II study.

      The Secondary Objective is to evaluate the pharmacokinetics (PK) of multiple dose oral
      administration of DTRMWXHS-12 capsule in patients with relapsed/refractory MCL.

      The Exploratory Objective is to preliminarily evaluate the efficacy of DTRMWXHS-12 capsule in
      patients with relapsed/refractory MCL.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Incidence and severity of (serious) adverse events n each patient according to the NCI-CTCAE4.03 grading
time frame: Starting from date of first dose up to 35 days after last dose
description: To monitor AEs and SAEs in each patient according to the NCI-CTCAE4.03 grading criteria by evaluating changes in physical examination, laboratory tests, and 12-lead ECG during the whole study
measure: concentration of drug in plasma
time frame: From date of first dose to day 56
description: concentration of drug in plasma
measure: Overall response rate (ORR)
time frame: From date of first dose to date of disease progression, an average of 6 months
description: Percentage of patients with PR, CR
arm group label: Experimental Treatment
arm group type: Experimental
description: DTRMWXHS-12, oral capsule, daily, 28 days as a cycle
intervention type: Drug
intervention name: DTRMWXHS-12
description: DTRMWXHS-12 capsules: 150 mg, 300 mg
arm group label: Experimental Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wei He, Ph.D.
role: Study Director
affiliation: Zhejiang DTRM Biopharma
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Mantle-Cell