<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/NCT02187133</url>
  </required_header>
  <id_info>
    <org_study_id>14251</org_study_id>
    <secondary_id>NCI-2015-00775</secondary_id>
    <nct_id>NCT02187133</nct_id>
  </id_info>
  <brief_title>Carfilzomib With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma</brief_title>
  <official_title>A Phase Ib Dose Escalation Trial of Carfilzomib in Combination With Bendamustine and Rituximab In Patients With Relapsed or Refractory Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Comprehensive Cancer Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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 study will be conducted as a Phase Ib, open-label, non-randomized, single-institution&#xD;
      study to evaluate the safety and tolerability of carfilzomib in combination with bendamustine&#xD;
      and rituximab in patients with relapsed or refractory NHL and to determine the recommended&#xD;
      phase II dose and preliminary efficacy of this combination. The study will have two phases: a&#xD;
      dose-escalation phase to determine the maximal tolerated dose of carfilzomib in this&#xD;
      combination where participants will be monitored for toxicity, tolerability and response and&#xD;
      a dose-expansion phase that will determine the preliminary efficacy in patients with Mantle&#xD;
      cell lymphoma or any other disease subtype in which there is a preliminary efficacy signal&#xD;
      observed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the safety and tolerability of carfilzomib when combined with bendamustine&#xD;
      (bendamustine hydrochloride) and rituximab in patients with relapsed or refractory&#xD;
      non-Hodgkin's lymphoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the preliminary antitumor activity of carfilzomib with bendamustine and&#xD;
      rituximab in patients with non-Hodgkin lymphoma (dose escalation) and with specific&#xD;
      non-Hodgkin lymphoma (NHL) subtypes (dose expansion).&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of carfilzomib.&#xD;
&#xD;
      Patients receive carfilzomib intravenously (IV) over 30 minutes twice weekly on days 1, 2, 8,&#xD;
      9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes&#xD;
      on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1&#xD;
      (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 weeks for 6 months,&#xD;
      every 3 months for 6 months, and then every 6 months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 5, 2015</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 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>Maximally tolerated dose (MTD)</measure>
    <time_frame>Up to 1 cycle (28 days per cycle)</time_frame>
    <description>The MTD will be the dose level immediately preceding the dose level at which &gt;= 2 Dose Limiting Toxicities (DLT) are observed and at which 0/3 or 1/6 participants experiences a DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with Dose Limiting Toxicities (DLT)</measure>
    <time_frame>Up to 1 cycle (28 days per cycle)</time_frame>
    <description>The DLT period will correspond to cycle 1 of therapy. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 will be used to assess the severity of adverse events. The causality of each AE will be assessed by the investigator for confirmation of a DLT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The lymphoma response assessment will be determined using the revised International Working Group (IWG) criteria for Complete Response (CR) defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, a post-treatment residual mass of any size is permitted as long as it is Positron Emission Tomography (PET) negative, the spleen and/or liver, if enlarged before therapy on the basis of the physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, etc. or Partial Response (PR) defined as the post-treatment PET should be positive in at least one previously involved site, At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, No new sites of disease should be observed, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of Response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined as the time from documentation of PR or CR until documented lymphoma progression or receipt of anti-lymphoma therapy or death due to lymphoma. Patients are to be censored at the time of last follow-up or death due to another cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression Free Survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined as the time from day 1 until lymphoma progression, receipt of anti-lymphoma therapy, or death as a result of any cause. Patients will be censored at the time of last follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Next Therapy</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Time to next therapy is measured from day 1 to receipt of anti-lymphoma therapy or death due to lymphoma. Patients are censored at the time of last follow-up or death unrelated to treatment or disease.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Median Overall Survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined as the time from day 1 until death as a result of any cause. Patients will be censored at the time of last follow-up</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of antitumor activity with markers of activation of the terminal unfolded protein response (UPR) or modulation of the apoptotic pathway in primary tumor tissue.</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The molecular events associated with the terminal UPR and apoptotic pathways will be correlated to assess their predictive utility for response to therapy with carfilzomib in combination with bendamustine.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of treatment-related toxicity with markers of activation of the terminal unfolded protein response (UPR) or modulation of the apoptotic pathway in primary tumor tissue.</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The molecular events associated with the terminal UPR and apoptotic pathways will be correlated to assess their predictive utility for response to toxicity with carfilzomib in combination with bendamustine.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Lymphoma, Non-Hodgkin</condition>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive carfilzomib IV over 30 minutes twice weekly on days 1, 2, 8, 9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1 (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Given IV; Dose Level (DL)&#xD;
Twice Weekly:&#xD;
DL -1 and DL 1: 15 mg/m^2&#xD;
Weekly:&#xD;
DL 1.5: 20,27,27 mg/m^2, DL 2: 20,36,36 mg/m^2, DL 3: 20,56,56 mg/m^2 DL 4: 20,70,70 mg/m^2</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Kyprolis</other_name>
    <other_name>PR-171</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bendamustine</intervention_name>
    <description>Given IV; Dose Level (DL)&#xD;
DL -1: 75 mg/m^2 DL 1,1.5, 2, 3, and 4: 90 mg/m^2</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Bendamustine Hydrochloride</other_name>
    <other_name>Cytostasan Hydrochloride</other_name>
    <other_name>Levacet</other_name>
    <other_name>Ribomustin</other_name>
    <other_name>Treanda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV; 375 mg/m^2</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>C2B8 Monoclonal Antibody</other_name>
    <other_name>Rituxan</other_name>
    <other_name>RTXM83</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically-confirmed B-cell non-Hodgkin's lymphoma (Mantle Cell Lymphoma,&#xD;
             Follicular Lymphoma, Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia, Marginal&#xD;
             Zone Lymphoma, Diffuse Large B-cell Lymphoma, and Lymphoplasmacytic Lymphoma)&#xD;
&#xD;
          -  Must have relapsed or refractory disease after 2 or more prior lines of therapy; 1&#xD;
             line of therapy is allowed, if it included an autologous stem cell transplant and at&#xD;
             least 12 weeks have elapsed from Day 0. A line of therapy is defined as a course of&#xD;
             therapy that is not interrupted by progressive disease.&#xD;
&#xD;
          -  Subjects must have measurable disease of at least 1.5 cm in diameter&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and&#xD;
             to practice contraception. FCBP definition: A female of childbearing potential is a&#xD;
             sexually mature woman who: 1) has not undergone a hysterectomy or bilateral&#xD;
             oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive&#xD;
             months.&#xD;
&#xD;
          -  Male subjects must agree to practice contraception for at least 90 days after the last&#xD;
             dose of carfilzomib, and must agree not to donate sperm for at least 90 days after the&#xD;
             last dose of carfilzomib&#xD;
&#xD;
        Adequate bone marrow function:&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1.0 × 10^9/L&#xD;
&#xD;
          -  Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior Cycle 1, Day 1 (subjects may be&#xD;
             receiving red blood cell (RBC) transfusions in accordance with institutional&#xD;
             guidelines)&#xD;
&#xD;
          -  Platelet count ≥ 75 × 10^9/L or≥ 50× 10^9/L if there is lymphoma involvement in the&#xD;
             bone marrow, independent of platelet transfusion&#xD;
&#xD;
        Adequate hepatic function:&#xD;
&#xD;
          -  Serum aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 3 times the&#xD;
             upper limit of normal&#xD;
&#xD;
          -  Serum direct bilirubin ≤ 2 mg/dL (unless history of Gilbert's)&#xD;
&#xD;
        Adequate renal function:&#xD;
&#xD;
          -  Creatinine clearance (CrCl) ≥ 30 mL/minute, either measured or calculated using a&#xD;
             standard formula (eg, Cockcroft and Gault)&#xD;
&#xD;
          -  Uric acid If elevated, corrected to within laboratory range prior to dosing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Progressive disease on bendamustine within 6 months of cycle 1, Day 1&#xD;
&#xD;
          -  Prior treatment with carfilzomib for lymphoma&#xD;
&#xD;
          -  Patient has received other investigational drugs within 21 days prior to Cycle 1, Day&#xD;
             1. Exceptions allowed if greater than four half-lives of the experimental agent ).&#xD;
&#xD;
          -  Prior radiation therapy or chemotherapy within 2 weeks prior Cycle 1, Day 1,&#xD;
             monoclonal antibody therapy within 4 weeks&#xD;
&#xD;
          -  Prior allogeneic transplant&#xD;
&#xD;
          -  Active, uncontrolled central nervous system (CNS) involvement by lymphoma&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Major surgery within 14 days prior Cycle 1, Day 1&#xD;
&#xD;
          -  Acute active infection requiring treatment (systemic antibiotics, antivirals, or&#xD;
             antifungals) within 14 days prior Cycle 1, Day 1&#xD;
&#xD;
          -  Known human immunodeficiency virus infection&#xD;
&#xD;
          -  Active hepatitis C infection (HCV), defined as presence of HCV antibody.&#xD;
&#xD;
          -  Unstable angina or myocardial infarction within 6 months prior Cycle 1, Day 1, New&#xD;
             York Heart Association (NYHA) Class III or IV heart failure, left ventricular ejection&#xD;
             fraction (LVEF) &lt; 40%, uncontrolled angina, history of severe coronary artery disease,&#xD;
             history of torsade de pointes, history of symptomatic pulmonary hypertension, severe&#xD;
             uncontrolled ventricular arrhythmias, sick sinus syndrome, QTc prolongation &gt;450 msec,&#xD;
             or electrocardiographic evidence of acute ischemia or Grade 3 conduction system&#xD;
             abnormalities unless subject has a pacemaker.&#xD;
&#xD;
          -  Uncontrolled hypertension or uncontrolled diabetes within 14 days prior Cycle 1, Day 1&#xD;
&#xD;
          -  Nonhematologic malignancy within the past 3 years with the exception of a) adequately&#xD;
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)&#xD;
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or&#xD;
             less with stable prostate-specific antigen levels; or d) cancer considered cured by&#xD;
             surgical resection or unlikely to impact survival during the duration of the study,&#xD;
             such as localized transitional cell carcinoma of the bladder or benign tumors of the&#xD;
             adrenal or pancreas&#xD;
&#xD;
          -  Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior Cycle&#xD;
             1, Day 1&#xD;
&#xD;
          -  Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize&#xD;
             carfilzomib)&#xD;
&#xD;
          -  Contraindication to any of the required concomitant drugs or supportive treatments,&#xD;
             including hypersensitivity to all anticoagulation and antiplatelet options, antiviral&#xD;
             drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment&#xD;
&#xD;
          -  Subjects with pleural effusions requiring thoracentesis or ascites requiring&#xD;
             paracentesis within 14 days prior Cycle 1, Day 1&#xD;
&#xD;
          -  Any other clinically significant medical disease or condition that, in the&#xD;
             Investigator's opinion, may interfere with protocol adherence or a subject's ability&#xD;
             to give informed consent.&#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>Charalambos Andreadis, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Davis</name>
      <address>
        <city>Davis</city>
        <state>California</state>
        <zip>95616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>April 21, 2021</last_update_submitted>
  <last_update_submitted_qc>April 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>C. Babis Andreadis</investigator_full_name>
    <investigator_title>Associate Professor of Clinical Medicine</investigator_title>
  </responsible_party>
  <keyword>Relapsed</keyword>
  <keyword>Refractory</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02187133
org study id: 14251
secondary id: NCI-2015-00775
nct id: NCT02187133
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will be conducted as a Phase Ib, open-label, non-randomized, single-institution
      study to evaluate the safety and tolerability of carfilzomib in combination with bendamustine
      and rituximab in patients with relapsed or refractory NHL and to determine the recommended
      phase II dose and preliminary efficacy of this combination. The study will have two phases: a
      dose-escalation phase to determine the maximal tolerated dose of carfilzomib in this
      combination where participants will be monitored for toxicity, tolerability and response and
      a dose-expansion phase that will determine the preliminary efficacy in patients with Mantle
      cell lymphoma or any other disease subtype in which there is a preliminary efficacy signal
      observed.
PRIMARY OBJECTIVES:

      I. To assess the safety and tolerability of carfilzomib when combined with bendamustine
      (bendamustine hydrochloride) and rituximab in patients with relapsed or refractory
      non-Hodgkin's lymphoma.

      SECONDARY OBJECTIVES:

      I. To evaluate the preliminary antitumor activity of carfilzomib with bendamustine and
      rituximab in patients with non-Hodgkin lymphoma (dose escalation) and with specific
      non-Hodgkin lymphoma (NHL) subtypes (dose expansion).

      OUTLINE: This is a dose-escalation study of carfilzomib.

      Patients receive carfilzomib intravenously (IV) over 30 minutes twice weekly on days 1, 2, 8,
      9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes
      on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1
      (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 weeks for 6 months,
      every 3 months for 6 months, and then every 6 months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximally tolerated dose (MTD)
time frame: Up to 1 cycle (28 days per cycle)
description: The MTD will be the dose level immediately preceding the dose level at which >= 2 Dose Limiting Toxicities (DLT) are observed and at which 0/3 or 1/6 participants experiences a DLT.
measure: Number of participants with Dose Limiting Toxicities (DLT)
time frame: Up to 1 cycle (28 days per cycle)
description: The DLT period will correspond to cycle 1 of therapy. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 will be used to assess the severity of adverse events. The causality of each AE will be assessed by the investigator for confirmation of a DLT.
measure: Overall Response Rate (ORR)
time frame: Up to 2 years
description: The lymphoma response assessment will be determined using the revised International Working Group (IWG) criteria for Complete Response (CR) defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, a post-treatment residual mass of any size is permitted as long as it is Positron Emission Tomography (PET) negative, the spleen and/or liver, if enlarged before therapy on the basis of the physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, etc. or Partial Response (PR) defined as the post-treatment PET should be positive in at least one previously involved site, At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, No new sites of disease should be observed, etc.
measure: Median Duration of Response
time frame: Up to 2 years
description: Defined as the time from documentation of PR or CR until documented lymphoma progression or receipt of anti-lymphoma therapy or death due to lymphoma. Patients are to be censored at the time of last follow-up or death due to another cause.
measure: Median Progression Free Survival (PFS)
time frame: Up to 2 years
description: Defined as the time from day 1 until lymphoma progression, receipt of anti-lymphoma therapy, or death as a result of any cause. Patients will be censored at the time of last follow up.
measure: Median Time to Next Therapy
time frame: Up to 2 years
description: Time to next therapy is measured from day 1 to receipt of anti-lymphoma therapy or death due to lymphoma. Patients are censored at the time of last follow-up or death unrelated to treatment or disease.
measure: Median Overall Survival
time frame: Up to 2 years
description: Defined as the time from day 1 until death as a result of any cause. Patients will be censored at the time of last follow-up
measure: Correlation of antitumor activity with markers of activation of the terminal unfolded protein response (UPR) or modulation of the apoptotic pathway in primary tumor tissue.
time frame: Up to 2 years
description: The molecular events associated with the terminal UPR and apoptotic pathways will be correlated to assess their predictive utility for response to therapy with carfilzomib in combination with bendamustine.
measure: Correlation of treatment-related toxicity with markers of activation of the terminal unfolded protein response (UPR) or modulation of the apoptotic pathway in primary tumor tissue.
time frame: Up to 2 years
description: The molecular events associated with the terminal UPR and apoptotic pathways will be correlated to assess their predictive utility for response to toxicity with carfilzomib in combination with bendamustine.
arm group label: Treatment
arm group type: Experimental
description: Patients receive carfilzomib IV over 30 minutes twice weekly on days 1, 2, 8, 9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1 (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Carfilzomib
description: Given IV; Dose Level (DL)
Twice Weekly:
DL -1 and DL 1: 15 mg/m^2
Weekly:
DL 1.5: 20,27,27 mg/m^2, DL 2: 20,36,36 mg/m^2, DL 3: 20,56,56 mg/m^2 DL 4: 20,70,70 mg/m^2
arm group label: Treatment
other name: Kyprolis
other name: PR-171
intervention type: Drug
intervention name: Bendamustine
description: Given IV; Dose Level (DL)
DL -1: 75 mg/m^2 DL 1,1.5, 2, 3, and 4: 90 mg/m^2
arm group label: Treatment
other name: Bendamustine Hydrochloride
other name: Cytostasan Hydrochloride
other name: Levacet
other name: Ribomustin
other name: Treanda
intervention type: Drug
intervention name: Rituximab
description: Given IV; 375 mg/m^2
arm group label: Treatment
other name: C2B8 Monoclonal Antibody
other name: Rituxan
other name: RTXM83
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charalambos Andreadis, M.D.
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: C. Babis Andreadis
investigator title: Associate Professor of Clinical Medicine
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Rituximab
mesh term: Bendamustine Hydrochloride
sharing ipd: No