<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/NCT03003546</url>
  </required_header>
  <id_info>
    <org_study_id>LS1681</org_study_id>
    <secondary_id>NCI-2016-01984</secondary_id>
    <secondary_id>P50CA097274</secondary_id>
    <nct_id>NCT03003546</nct_id>
  </id_info>
  <brief_title>Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma, LS1681 Trial</brief_title>
  <official_title>LS1681: A Phase I Trial of AR160 (Abraxane/Rituximab 160nm Nanoparticle) in Relapsed/Refractory B Cell Lymphomas Including Transformed Follicular Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the best dose and side effects of paclitaxel albumin-stabilized&#xD;
      nanoparticle formulation (nab-paclitaxel)/rituximab-coated nanoparticle AR160 in treating&#xD;
      patients with B-cell non-Hodgkin lymphoma that has come back (relapsed) or is not responding&#xD;
      to treatment (refractory). Nab-paclitaxel/rituximab-coated nanoparticle AR160 is a&#xD;
      combination of paclitaxel albumin-stabilized nanoparticle formulation and rituximab. Drugs&#xD;
      used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in&#xD;
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Immunotherapy with rituximab, may&#xD;
      induce changes in body's immune system and may interfere with the ability of tumor cells to&#xD;
      grow and spread. Giving paclitaxel albumin-stabilized nanoparticle formulation and rituximab&#xD;
      may work better in treating patients with B-cell non-Hodgkin lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To establish the maximum tolerated dose (MTD) of nab-paclitaxel/rituximab-coated&#xD;
      nanoparticle AR160 (AR160) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma&#xD;
      (NHL). (Phase I)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the toxicity and safety of AR160. II. To assess complete response rate (CR)&#xD;
      progression free survival (PFS), and overall survival (OS) of AR160 with relapsed/refractory&#xD;
      B-cell NHL.&#xD;
&#xD;
      CORRELATIVE RESEARCH OBJECTIVE:&#xD;
&#xD;
      I. Evaluate pharmacokinetics (PK) of AR160 in two formal PK studies, dose 1 of cycle 1 (48&#xD;
      hours [h] PK analysis) and dose 1 of cycle 2 (24h PK analysis). As of Amendment 4, PKs will&#xD;
      no longer be collected.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study.&#xD;
&#xD;
      Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 intravenously (IV) over&#xD;
      30-60 minutes on days 1, 8, and 15. Cycles repeat every 28 days for up to 12 cycles in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for up to 2&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 25, 2019</start_date>
  <completion_date type="Actual">May 16, 2023</completion_date>
  <primary_completion_date type="Actual">May 16, 2023</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>Maximum tolerated dose (MTD)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>MTD will be defined as the highest dose level patients develop a dose limiting toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be assessed using the Lugano Classification Response criteria. A table will be constructed to display by dose level, the number of patients treated at that dose level, the number of cycles of treatment administered, dose limiting toxicity (DLT) observed, and number of responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years</time_frame>
    <description>The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Time from registration to death due to any cause, assessed up to 2 years</time_frame>
    <description>The distribution of overall survival will be estimated using the method of Kaplan Meier.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Recurrent Aggressive Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Small Lymphocytic Lymphoma</condition>
  <condition>Refractory Aggressive Non-Hodgkin Lymphoma</condition>
  <condition>Refractory B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (AR160)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 IV over 30-60 minutes on days 1, 8, and 15. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (AR160)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel/Rituximab-coated Nanoparticle AR160</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (AR160)</arm_group_label>
    <other_name>Abraxane coated with Rituximab</other_name>
    <other_name>Abraxane Coated with Rituximab 160nm Nanoparticle</other_name>
    <other_name>Abraxane/Rituxan 160 Complex</other_name>
    <other_name>AR160</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (AR160)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;= 18 years.&#xD;
&#xD;
          -  Histological confirmation of relapsed/refractory B-cell NHL, CD20+&#xD;
&#xD;
               -  NOTE: patients with small lymphocytic lymphoma (SLL) are eligible however&#xD;
                  patients with chronic lymphocytic leukemia (CLL) are not eligible&#xD;
&#xD;
               -  Waldenstrom macroglobulinemia patients are not eligible; aggressive lymphoma&#xD;
                  patients who are transplant eligible must have undergone a transplant&#xD;
&#xD;
               -  The biopsy confirming relapse can be up to 24 weeks prior to registration as long&#xD;
                  as there is no intervening therapy&#xD;
&#xD;
          -  Measurable disease (at least 1 lesion of &gt;= 1.5 cm in one diameter) as detected by&#xD;
             computed tomography (CT) or the CT images of the positron emission tomography&#xD;
             (PET)/CT. Skins lesions can be used if the area is greater than or equal to 2 cm in at&#xD;
             least one diameter and photographed with a ruler&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3 (obtained =&lt; 14 days prior to&#xD;
             registration)&#xD;
&#xD;
          -  Platelet count &gt;= 75,000/mm^3 (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Hemoglobin &gt;= 8.0 g/dL (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 X upper limit of normal (ULN) or if total bilirubin is &gt; 1.5 X&#xD;
             ULN, the direct bilirubin =&lt; ULN (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 3 X ULN unless due to direct lymphoma involvement, and then =&lt;&#xD;
             5 X ULN (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Aspartate transaminase (AST) =&lt; 3 X ULN unless due to direct lymphoma involvement, and&#xD;
             then =&lt; 5 X ULN (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Calculated creatinine clearance must be &gt;= 30 ml/min using the Cockcroft-Gault formula&#xD;
             (obtained =&lt; 14 days prior to registration)&#xD;
&#xD;
          -  Life expectancy &gt;= 3 months&#xD;
&#xD;
          -  Ability to provide written informed consent&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up (during the treatment phase&#xD;
             of the study)&#xD;
&#xD;
          -  Willing to provide blood samples for correlative research purposes&#xD;
&#xD;
          -  Failed or are intolerant to 2 or more lines of established therapy or for whom no&#xD;
             other treatment options are available in the opinion of the investigator&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Disease-free of prior invasive malignancies for &gt; 5 years prior to registration&#xD;
&#xD;
               -  Note: Exception of curatively-treated basal cell or squamous cell carcinoma of&#xD;
                  the skin or carcinoma in situ of the cervix&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following because this study involves an investigational agent whose&#xD;
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are&#xD;
             unknown:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          -  Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with&#xD;
             malignant lymphoma cells that requires therapy&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment&#xD;
             of the investigator, would make the patient inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Received most recent therapy =&lt; 4 weeks prior to registration; NOTE: use of systemic&#xD;
             steroid therapy is allowed pretreatment&#xD;
&#xD;
          -  Receiving any other investigational agent which would be considered as a treatment for&#xD;
             the primary neoplasm&#xD;
&#xD;
          -  Patients with &gt;= 25% of the bone marrow radiated for other diseases&#xD;
&#xD;
          -  Other medical conditions including but not limited to:&#xD;
&#xD;
               -  History of liver disease such as cirrhosis, chronic active hepatitis, chronic&#xD;
                  persistent hepatitis or hepatitis B or C&#xD;
&#xD;
               -  Active infection requiring parenteral antibiotics&#xD;
&#xD;
               -  New York Heart Association class II-IV congestive heart failure (serious cardiac&#xD;
                  arrhythmia requiring medication)&#xD;
&#xD;
               -  Myocardial infarction or unstable angina =&lt; 6 months prior to registration&#xD;
&#xD;
               -  Congestive heart failure requiring use of ongoing maintenance therapy for&#xD;
                  life-threatening ventricular arrhythmias&#xD;
&#xD;
               -  Clinically significant peripheral vascular disease&#xD;
&#xD;
               -  History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.),&#xD;
                  clinically significant stroke or transient ischemic attack (TIA) =&lt; 6 months&#xD;
                  prior to registration, seizures not controlled with standard medical therapy&#xD;
&#xD;
               -  Neuropathy ˃ grade 3&#xD;
&#xD;
          -  Administration of strong CYP2C8 or CYP3A4 inhibitors or inducers =&lt; 10 days prior to&#xD;
             registration&#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_official>
    <last_name>Thomas M Habermann</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic in Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 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, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Recurrence</mesh_term>
    <mesh_term>Aggression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</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/NCT03003546
org study id: LS1681
secondary id: NCI-2016-01984
secondary id: P50CA097274
nct id: NCT03003546
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the best dose and side effects of paclitaxel albumin-stabilized
      nanoparticle formulation (nab-paclitaxel)/rituximab-coated nanoparticle AR160 in treating
      patients with B-cell non-Hodgkin lymphoma that has come back (relapsed) or is not responding
      to treatment (refractory). Nab-paclitaxel/rituximab-coated nanoparticle AR160 is a
      combination of paclitaxel albumin-stabilized nanoparticle formulation and rituximab. Drugs
      used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Immunotherapy with rituximab, may
      induce changes in body's immune system and may interfere with the ability of tumor cells to
      grow and spread. Giving paclitaxel albumin-stabilized nanoparticle formulation and rituximab
      may work better in treating patients with B-cell non-Hodgkin lymphoma.
PRIMARY OBJECTIVE:

      I. To establish the maximum tolerated dose (MTD) of nab-paclitaxel/rituximab-coated
      nanoparticle AR160 (AR160) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
      (NHL). (Phase I)

      SECONDARY OBJECTIVES:

      I. To assess the toxicity and safety of AR160. II. To assess complete response rate (CR)
      progression free survival (PFS), and overall survival (OS) of AR160 with relapsed/refractory
      B-cell NHL.

      CORRELATIVE RESEARCH OBJECTIVE:

      I. Evaluate pharmacokinetics (PK) of AR160 in two formal PK studies, dose 1 of cycle 1 (48
      hours [h] PK analysis) and dose 1 of cycle 2 (24h PK analysis). As of Amendment 4, PKs will
      no longer be collected.

      OUTLINE: This is a dose-escalation study.

      Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 intravenously (IV) over
      30-60 minutes on days 1, 8, and 15. Cycles repeat every 28 days for up to 12 cycles in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for up to 2
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: Up to 28 days
description: MTD will be defined as the highest dose level patients develop a dose limiting toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.
measure: Tumor response
time frame: Up to 2 years
description: Will be assessed using the Lugano Classification Response criteria. A table will be constructed to display by dose level, the number of patients treated at that dose level, the number of cycles of treatment administered, dose limiting toxicity (DLT) observed, and number of responses.
measure: Progression free survival
time frame: Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years
description: The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
measure: Overall survival
time frame: Time from registration to death due to any cause, assessed up to 2 years
description: The distribution of overall survival will be estimated using the method of Kaplan Meier.
arm group label: Treatment (AR160)
arm group type: Experimental
description: Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 IV over 30-60 minutes on days 1, 8, and 15. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (AR160)
intervention type: Drug
intervention name: Nab-paclitaxel/Rituximab-coated Nanoparticle AR160
description: Given IV
arm group label: Treatment (AR160)
other name: Abraxane coated with Rituximab
other name: Abraxane Coated with Rituximab 160nm Nanoparticle
other name: Abraxane/Rituxan 160 Complex
other name: AR160
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (AR160)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas M Habermann
role: Principal Investigator
affiliation: Mayo Clinic in Rochester
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, B-Cell
mesh term: Recurrence
mesh term: Aggression
mesh term: Paclitaxel
mesh term: Rituximab
mesh term: Albumin-Bound Paclitaxel