<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/NCT01685008</url>
  </required_header>
  <id_info>
    <org_study_id>MOR208C201</org_study_id>
    <secondary_id>2012-002659-41</secondary_id>
    <nct_id>NCT01685008</nct_id>
  </id_info>
  <brief_title>Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin's Lymphoma (NHL)</brief_title>
  <official_title>A Phase IIa, Open-label, Multicenter Study of Single-agent MOR00208, an Fc-optimized Anti-CD19 Antibody, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MorphoSys AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MorphoSys AG</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multicenter study to characterize the safety and efficacy of the human&#xD;
      anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma&#xD;
      (NHL) who have received at least 1 prior therapy containing rituximab (at least once).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study enrols patients from four different NHL subtypes: follicular lymphoma (FL), diffuse&#xD;
      large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and other indolent NHL (iNHL). The&#xD;
      study will employ a two-stage design where the decision to further enrol any NHL subtype in&#xD;
      stage 2 will depend on best responses after two or three cycles in stage 1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2013</start_date>
  <completion_date type="Actual">April 6, 2022</completion_date>
  <primary_completion_date type="Actual">April 6, 2022</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>Overall response rate (ORR)</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>Proportion of Patients with Complete Response (CR) or Partial Response (PR), assessed as per the 2007 International Working Group (IWG) response criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stable Disease (SD) Rate</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>Proportion of Patients with Stable Disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>Time from first CR or PR to first documentation of relapse/progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>Time from first dosing until documentation of progression or death due to lymphoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>Time from first dosing until progression or death due to any case</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events (AEs)</measure>
    <time_frame>From first dose until 30 days after last dose of MOR00208, up to 4.5 years</time_frame>
    <description>Number of patients with AEs rated Mild, Moderate, and Severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and proportion of patients who potentially develop anti-MOR00208 antibodies and semiquantitative anti-MOR00208 antibody assessments</measure>
    <time_frame>From first dose until Follow-up Visit 3, up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) parameter: Maximum serum concentration observed (Cmax) of MOR00208</measure>
    <time_frame>Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)</time_frame>
    <description>The highest concentration of MOR00208 measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Time to maximum serum concentration observed (tmax) of MOR00208</measure>
    <time_frame>Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)</time_frame>
    <description>The time to highest concentration of MOR00208 measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Apparent trough serum concentration before dosing (Clast) of MOR00208</measure>
    <time_frame>Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)</time_frame>
    <description>The last quantifiable concentration from the first dose of MOR00208</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Area under the concentration curve from dose time zero to the time the last quantifiable concentration is observed (AUC[0-t]) of MOR00208</measure>
    <time_frame>Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)</time_frame>
    <description>Area under the concentration curve. The time curve from time zero (0) to the time that the last concentration above the lower limit of quantification (LLQ) is observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Area under the concentration curve from dose time zero to infinity (AUC[0-inf]) of MOR00208</measure>
    <time_frame>Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])</time_frame>
    <description>Area under the concentration curve. The time curve from time zero (0) to infinity (inf), where infinity is computed from AUC0-t + [Ct/λZ)]. Ct is calculated from the concentration at the last sampling time at which the sample is above LLQ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Apparent terminal rate constant (λz) of MOR00208</measure>
    <time_frame>Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])</time_frame>
    <description>Apparent terminal rate constant calculated from the regression analysis (slope) from the log-transformed measured concentrations on the terminal phase of the time-point concentration curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Apparent terminal half-life (t[1/2]) of MOR00208</measure>
    <time_frame>Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])</time_frame>
    <description>Apparent terminal half-life calculated from ln(2)/λz</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Total body clearance (CL) of MOR00208</measure>
    <time_frame>Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])</time_frame>
    <description>Total body clearance calculated for single or multiple doses: dose(s)/AUC(0-inf)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter: Apparent volume of distribution (Vz) of MOR00208</measure>
    <time_frame>Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])</time_frame>
    <description>Apparent volume of distribution during the terminal phase, calculated from dose/(AUC(0-inf)*λz)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change from Baseline in measurements of B-, T- and NK cell populations</measure>
    <time_frame>Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 4.5 years)</time_frame>
    <description>Actual change from baseline will be summarized descriptively by visit for the pharmacodynamic parameters B-, T-, and NK cell populations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from Baseline in measurements of B-, T- and NK cell populations</measure>
    <time_frame>Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 4.5 years)</time_frame>
    <description>Percent change from baseline will be summarized descriptively by visit for the pharmacodynamic parameters B-, T-, and NK cell populations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of AEs stratified by Baseline CD19 expression on malignant lymphoma cells</measure>
    <time_frame>From first dose until 30 days after last dose of MOR00208, up to 4.5 years</time_frame>
    <description>Incidence of AEs as stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of ORR stratified by Baseline CD19 expression on malignant lymphoma cells</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>The analysis of the primary endpoint (ORR) will additionally be stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of AEs stratified by FcγRIIIa and FcγRIIa polymorphism</measure>
    <time_frame>From first dose until 30 days after last dose of MOR00208, up to 4.5 years</time_frame>
    <description>Incidence of AEs as stratified by FcγRIIIa and FcγRIIa polymorphism subgroups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of ORR stratified by FcγRIIIa and FcγRIIa polymorphism</measure>
    <time_frame>From first dose throughout the study, up to 4.5 years</time_frame>
    <description>The analysis of the primary endpoint (ORR) will additionally be stratified by FcγRIIIa and FcγRIIa polymorphism subgroups</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>MOR00208 (formerly Xmab5574)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous Infusion of MOR00208, Fc-Optimized Anti-CD19 Antibody</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MOR00208 (formerly Xmab 5574)</intervention_name>
    <arm_group_label>MOR00208 (formerly Xmab5574)</arm_group_label>
    <other_name>MOR208</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients ≥ 18 years of age.&#xD;
&#xD;
          2. Histologically-confirmed diagnosis according to Revised European American&#xD;
             Lymphoma/World Health Organization classification, of the following B-cell lymphomas:&#xD;
&#xD;
               1. FL&#xD;
&#xD;
               2. MCL&#xD;
&#xD;
               3. DLBCL&#xD;
&#xD;
               4. Other indolent NHL (eg, MZL/MALT)&#xD;
&#xD;
          3. Patients' NHL must have progressed after at least 1 prior rituximab containing&#xD;
             regimen.&#xD;
&#xD;
          4. One site of measurable disease by magnetic resonance imaging (MRI) or computed&#xD;
             tomography (CT) scan defined as at least one lesion that measures at least 1.5 × 1.5&#xD;
             cm.&#xD;
&#xD;
             Exception:&#xD;
&#xD;
             For patients with MCL only, patients with nonmeasurable disease but evaluable sites&#xD;
             (bone marrow, spleen, peripheral blood, gastrointestinal tract) can be enrolled.&#xD;
&#xD;
          5. Patients who have previously received an autologous stem cell transplantation must be&#xD;
             at least 4 weeks post-transplant before study drug administration and must have&#xD;
             exhibited a full haematological recovery.&#xD;
&#xD;
          6. Discontinued previous monoclonal antibody therapy (except rituximab) or&#xD;
             radioimmunotherapy administration for at least 60 days before study drug&#xD;
             administration.&#xD;
&#xD;
          7. Off rituximab for at least 14 days before the screening visit and be confirmed to have&#xD;
             either no response or have disease progression after rituximab treatment.&#xD;
&#xD;
          8. Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission&#xD;
             tomography (FDG-PET) scan at baseline (Cheson 2007 response criteria).&#xD;
&#xD;
          9. Life expectancy of &gt; 3 months.&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group (ECOG) performance status of &lt; 3.&#xD;
&#xD;
         11. Laboratory criteria at screening:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L&#xD;
&#xD;
               2. Platelet count ≥ 75 × 10⁹/L without previous transfusion within 10 days of first&#xD;
                  study drug administration&#xD;
&#xD;
               3. Haemoglobin ≥ 8.0 g/dL (may have been transfused)&#xD;
&#xD;
               4. Serum creatinine &lt; 2.0 x upper limit of normal (ULN)&#xD;
&#xD;
               5. Total bilirubin ≤ 2.0 × ULN&#xD;
&#xD;
               6. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN&#xD;
&#xD;
         12. If a female of childbearing potential, a negative pregnancy test must be confirmed&#xD;
             before enrolment and use of double-barrier contraception or oral contraceptive plus&#xD;
             barrier contraceptive must be used during the study and for 3 months after the last&#xD;
             dose, or confirmation of having undergone clinically documented total hysterectomy&#xD;
             and/or oophorectomy, tubal ligation.&#xD;
&#xD;
         13. If a male, an effective barrier method of contraception must be used during the study&#xD;
             and for 3 months after the last dose if the patient is sexually active with a female&#xD;
             of childbearing potential.&#xD;
&#xD;
         14. Able to comply with all study-related procedures, medication use, and evaluations.&#xD;
&#xD;
         15. Able to understand and give written informed consent and comply with the study&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with cytotoxic chemotherapy, immunotherapy, radiotherapy or other&#xD;
             lymphoma specific therapy within 14 days before the screening visit or patient has not&#xD;
             recovered from side effects of previous lymphoma-specific therapy.&#xD;
&#xD;
          2. Treatment with a systemic investigational agent within 28 days before the screening&#xD;
             visit.&#xD;
&#xD;
          3. Previous treatment with an anti-CD19 antibody or fragments.&#xD;
&#xD;
          4. Previous allogenic stem cell transplantation.&#xD;
&#xD;
          5. Known or suspected hypersensitivity to the excipients contained in the study drug&#xD;
             formulation.&#xD;
&#xD;
          6. Clinically significant cardiovascular disease or cardiac insufficiency,&#xD;
             cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial&#xD;
             infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.&#xD;
&#xD;
          7. Patients with positive hepatitis serology:&#xD;
&#xD;
             Hepatitis B (HBV): Patients with positive serology for HBV defined as positivity for&#xD;
             hepatitis B surface antigen (HBsAg) or total anti-hepatitis B core antibody&#xD;
             (anti-HBc). Patients positive for anti-HBc may be included if HBV DNA is not&#xD;
             detectable.&#xD;
&#xD;
             Hepatitis C (HCV): Patients positive HCV serology (defined as positive for anti-HCV&#xD;
             antibody [anti-HCV]) unless HCV-ribonucleic acid (RNA) is confirmed negative.&#xD;
&#xD;
          8. History of HIV infection.&#xD;
&#xD;
          9. Any active systemic infection (viral, fungal, or bacterial) requiring active&#xD;
             parenteral antibiotic therapy within 4 weeks of study drug administration.&#xD;
&#xD;
         10. Current treatment with immunosuppressive agents other than prescribed corticosteroids&#xD;
             (not more than 10-mg prednisone equivalent).&#xD;
&#xD;
         11. Major surgery or radiation therapy within 4 weeks before first study drug&#xD;
             administration.&#xD;
&#xD;
         12. Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study&#xD;
             treatment in the investigator's opinion.&#xD;
&#xD;
         13. History or clinical evidence of central nervous system (CNS), meningeal, or epidural&#xD;
             disease, including brain metastasis.&#xD;
&#xD;
         14. Active treatment/chemotherapy for another primary malignancy within the past 5 years&#xD;
             (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer&#xD;
             not requiring treatment, and cervical carcinoma in situ).&#xD;
&#xD;
         15. Pregnancy or breastfeeding in women and women of childbearing potential not using an&#xD;
             acceptable method of birth control.&#xD;
&#xD;
         16. History of noncompliance to medical regimens or patients who are considered&#xD;
             potentially unreliable not cooperative.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Norwalk</city>
        <state>Connecticut</state>
        <zip>06856</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Brussels #1</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Brussels #2</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Ulm</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Budapest #1</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Budapest #2</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Debrecen</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Chorzów</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Lódz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Slupsk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Madrid #1</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Madrid #2</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MorphoSys Research Site</name>
      <address>
        <city>Madrid #3</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morphosys Research Site</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 3, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</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 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NHL</keyword>
  <keyword>CD19</keyword>
  <keyword>MOR208</keyword>
  <keyword>MOR00208</keyword>
  <keyword>Xmab5574</keyword>
  <keyword>B-Cell Non-Hodgkin´s Lymphoma</keyword>
  <keyword>Fc-optimized Anti-CD19 Antibody</keyword>
  <keyword>Tafasitamab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>April 5, 2023</submitted>
    <returned>April 26, 2023</returned>
    <submitted>June 7, 2023</submitted>
    <returned>June 28, 2023</returned>
  </pending_results>
  <!-- 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/NCT01685008
org study id: MOR208C201
secondary id: 2012-002659-41
nct id: NCT01685008
lead sponsor: 
has dmc: No
This is an open-label, multicenter study to characterize the safety and efficacy of the human
      anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma
      (NHL) who have received at least 1 prior therapy containing rituximab (at least once).
The study enrols patients from four different NHL subtypes: follicular lymphoma (FL), diffuse
      large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and other indolent NHL (iNHL). The
      study will employ a two-stage design where the decision to further enrol any NHL subtype in
      stage 2 will depend on best responses after two or three cycles in stage 1.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate (ORR)
time frame: From first dose throughout the study, up to 4.5 years
description: Proportion of Patients with Complete Response (CR) or Partial Response (PR), assessed as per the 2007 International Working Group (IWG) response criteria
measure: Stable Disease (SD) Rate
time frame: From first dose throughout the study, up to 4.5 years
description: Proportion of Patients with Stable Disease
measure: Duration of Response (DoR)
time frame: From first dose throughout the study, up to 4.5 years
description: Time from first CR or PR to first documentation of relapse/progression
measure: Time to Progression (TTP)
time frame: From first dose throughout the study, up to 4.5 years
description: Time from first dosing until documentation of progression or death due to lymphoma
measure: Progression-free Survival (PFS)
time frame: From first dose throughout the study, up to 4.5 years
description: Time from first dosing until progression or death due to any case
measure: Incidence and severity of adverse events (AEs)
time frame: From first dose until 30 days after last dose of MOR00208, up to 4.5 years
description: Number of patients with AEs rated Mild, Moderate, and Severe
measure: Number and proportion of patients who potentially develop anti-MOR00208 antibodies and semiquantitative anti-MOR00208 antibody assessments
time frame: From first dose until Follow-up Visit 3, up to 7 months
measure: Pharmacokinetic (PK) parameter: Maximum serum concentration observed (Cmax) of MOR00208
time frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)
description: The highest concentration of MOR00208 measured in serum
measure: PK parameter: Time to maximum serum concentration observed (tmax) of MOR00208
time frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)
description: The time to highest concentration of MOR00208 measured in serum
measure: PK parameter: Apparent trough serum concentration before dosing (Clast) of MOR00208
time frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)
description: The last quantifiable concentration from the first dose of MOR00208
measure: PK parameter: Area under the concentration curve from dose time zero to the time the last quantifiable concentration is observed (AUC[0-t]) of MOR00208
time frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)
description: Area under the concentration curve. The time curve from time zero (0) to the time that the last concentration above the lower limit of quantification (LLQ) is observed.
measure: PK parameter: Area under the concentration curve from dose time zero to infinity (AUC[0-inf]) of MOR00208
time frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])
description: Area under the concentration curve. The time curve from time zero (0) to infinity (inf), where infinity is computed from AUC0-t + [Ct/λZ)]. Ct is calculated from the concentration at the last sampling time at which the sample is above LLQ.
measure: PK parameter: Apparent terminal rate constant (λz) of MOR00208
time frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])
description: Apparent terminal rate constant calculated from the regression analysis (slope) from the log-transformed measured concentrations on the terminal phase of the time-point concentration curve
measure: PK parameter: Apparent terminal half-life (t[1/2]) of MOR00208
time frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])
description: Apparent terminal half-life calculated from ln(2)/λz
measure: PK parameter: Total body clearance (CL) of MOR00208
time frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])
description: Total body clearance calculated for single or multiple doses: dose(s)/AUC(0-inf)
measure: PK parameter: Apparent volume of distribution (Vz) of MOR00208
time frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])
description: Apparent volume of distribution during the terminal phase, calculated from dose/(AUC(0-inf)*λz)
measure: Absolute change from Baseline in measurements of B-, T- and NK cell populations
time frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 4.5 years)
description: Actual change from baseline will be summarized descriptively by visit for the pharmacodynamic parameters B-, T-, and NK cell populations.
measure: Percent change from Baseline in measurements of B-, T- and NK cell populations
time frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 4.5 years)
description: Percent change from baseline will be summarized descriptively by visit for the pharmacodynamic parameters B-, T-, and NK cell populations.
measure: Evaluation of AEs stratified by Baseline CD19 expression on malignant lymphoma cells
time frame: From first dose until 30 days after last dose of MOR00208, up to 4.5 years
description: Incidence of AEs as stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening
measure: Evaluation of ORR stratified by Baseline CD19 expression on malignant lymphoma cells
time frame: From first dose throughout the study, up to 4.5 years
description: The analysis of the primary endpoint (ORR) will additionally be stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening
measure: Evaluation of AEs stratified by FcγRIIIa and FcγRIIa polymorphism
time frame: From first dose until 30 days after last dose of MOR00208, up to 4.5 years
description: Incidence of AEs as stratified by FcγRIIIa and FcγRIIa polymorphism subgroups
measure: Evaluation of ORR stratified by FcγRIIIa and FcγRIIa polymorphism
time frame: From first dose throughout the study, up to 4.5 years
description: The analysis of the primary endpoint (ORR) will additionally be stratified by FcγRIIIa and FcγRIIa polymorphism subgroups
arm group label: MOR00208 (formerly Xmab5574)
arm group type: Experimental
description: intravenous Infusion of MOR00208, Fc-Optimized Anti-CD19 Antibody
intervention type: Drug
intervention name: MOR00208 (formerly Xmab 5574)
arm group label: MOR00208 (formerly Xmab5574)
other name: MOR208
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Belgium
country: Germany
country: Hungary
country: Italy
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
submitted: April 5, 2023
returned: April 26, 2023
submitted: June 7, 2023
returned: June 28, 2023