<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/NCT01729091</url>
  </required_header>
  <id_info>
    <org_study_id>2011-0379</org_study_id>
    <secondary_id>NCI-2014-01096</secondary_id>
    <secondary_id>RV-MM-PI-0691</secondary_id>
    <secondary_id>NCI-2014-00541</secondary_id>
    <secondary_id>2011-0379</secondary_id>
    <nct_id>NCT01729091</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma</brief_title>
  <official_title>Phase II Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</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 II trial studies the side effects and best dose of umbilical cord blood-derived&#xD;
      natural killer cells when given together with elotuzumab, lenalidomide, and high dose&#xD;
      melphalan before autologous stem cell transplant and to see how well they work in treating&#xD;
      patients with multiple myeloma. Before transplant, stem cells are taken from patients and&#xD;
      stored. Immunotherapy with monoclonal antibodies, such as elotuzumab, may induce changes in&#xD;
      the body's immune system and may interfere with the ability of cancer cells to grow and&#xD;
      spread. Drugs used in chemotherapy, such as lenalidomide and melphalan, may work in different&#xD;
      ways to stop the growth of tumor cells, either by killing the cells, by stopping them from&#xD;
      dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell&#xD;
      transplant stops the growth of cancer cells by stopping them from dividing or killing them.&#xD;
      Giving natural killer cells from donor umbilical cord blood before transplant may also kill&#xD;
      myeloma cells that remain in the body after the last chemotherapy treatment. After treatment,&#xD;
      stem cells are then returned to the patient to replace the blood-forming cells that were&#xD;
      destroyed by the chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To find the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived natural&#xD;
      killer (NK) cells.&#xD;
&#xD;
      II. To determine efficacy by the percent of patients achieving very good partial remission&#xD;
      (VGPR) + complete remission (CR) at 3 months post-transplant.&#xD;
&#xD;
      III. To assess the minimal residual disease rate 100 days post-transplant in high-risk&#xD;
      patients.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To quantify duration of infused allogeneic donor UCB-derived NK cells in the recipient.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of UCB-derived NK cells.&#xD;
&#xD;
      Patients receive elotuzumab intravenously (IV) over 2-5 hours on day -15 and -8, lenalidomide&#xD;
      orally (PO) once daily (QD) on days -8 to -2, high-dose melphalan IV over 30 minutes on day&#xD;
      -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell&#xD;
      transplant on day 0.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30, 60 and 100 days and 6&#xD;
      and 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 10, 2013</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells</measure>
    <time_frame>Within 30 days post-transplant</time_frame>
    <description>Defined as the highest dose for which the probability of toxicity is closest to 20%. Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of patients achieving very good partial response (VGPR) + complete response (CR)</measure>
    <time_frame>At 3 months post-transplant</time_frame>
    <description>Response will be tabulated by dose. Logistic regression methods will be used to model the rate of VGPR + CR as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities). Will estimate with a 95 percent credible interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Minimal residual disease (MRD) rate</measure>
    <time_frame>At 100 days</time_frame>
    <description>Will model the MRD rate in high-risk patients using logistical regression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>OS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model OS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>PFS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model PFS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be reported as an average time value with standard deviation. These data may also be used as covariates in the regression models.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Plasma Cell Leukemia</condition>
  <condition>Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Autologous Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo autologous stem cell transplant</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
    <other_name>Autologous Hematopoietic Cell Transplantation</other_name>
    <other_name>autologous stem cell transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
    <other_name>BMS-901608</other_name>
    <other_name>Empliciti</other_name>
    <other_name>HuLuc-63</other_name>
    <other_name>HuLuc63</other_name>
    <other_name>PDL-063</other_name>
    <other_name>PDL063</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
    <other_name>Alanine Nitrogen Mustard</other_name>
    <other_name>CB-3025</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-Phenylalanine Mustard</other_name>
    <other_name>L-sarcolysin</other_name>
    <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysine</other_name>
    <other_name>Melphalanum</other_name>
    <other_name>Phenylalanine Mustard</other_name>
    <other_name>Phenylalanine nitrogen mustard</other_name>
    <other_name>Sarcoclorin</other_name>
    <other_name>Sarkolysin</other_name>
    <other_name>WR-19813</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Natural Killer Cell Therapy</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Umbilical Cord Blood-Derived Lymphocyte Therapy</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, UCB-derived NK cells, transplant)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with high risk multiple myeloma who are transplant candidates, in partial&#xD;
             response (PR) or better; high risk will be defined as patients with any of the&#xD;
             following:&#xD;
&#xD;
               -  Fluorescence in situ hybridization showing t(4:14), t(14:16), t(14:20), gain&#xD;
                  (amp) 1q; deletion (Del) 17/17p [or tp53 gene mutation/deletion by next&#xD;
                  generation sequencing (NGS), or by conventional cytogenetics];&#xD;
&#xD;
               -  Deletion 13 by conventional cytogenetic analysis;&#xD;
&#xD;
               -  High risk signatures as determined by the GEP-70 or EMC-92 gene expression&#xD;
                  profiles;&#xD;
&#xD;
               -  Relapsed disease within 18 months of prior autologous stem cell transplant (ASCT)&#xD;
&#xD;
          -  Patients with plasma cell leukemia who are transplant candidates&#xD;
&#xD;
          -  Performance score of at least 70% by Karnofsky or 0 to 2 Eastern Cooperative Oncology&#xD;
             Group (ECOG)&#xD;
&#xD;
          -  Left ventricular ejection fraction greater than 40%&#xD;
&#xD;
          -  Pulmonary function test (PFT) demonstrating a diffusion capacity of least 40%&#xD;
             predicted&#xD;
&#xD;
          -  Estimated serum creatinine clearance &gt;= 60 ml/min (using the Cockcroft-Gault formula&#xD;
             and/or serum creatinine =&lt; 1.6 mg/dL&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) less than 3 x upper limit of normal&#xD;
&#xD;
          -  Total bilirubin less than 2 x upper limit of normal&#xD;
&#xD;
          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation&#xD;
             and Mitigation Strategy (REMS) program, and be willing and able to comply with the&#xD;
             requirements of the Revlimid REMS program&#xD;
&#xD;
          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as&#xD;
             required in the Revlimid REMS program&#xD;
&#xD;
          -  Men must agree to use a latex condom during sexual contact with females of child&#xD;
             bearing potential even if they have had a successful vasectomy&#xD;
&#xD;
          -  Patients must have a cord blood (CB) unit available which is matched with the patient&#xD;
             at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular)&#xD;
             antigens&#xD;
&#xD;
          -  Patient or legally authorized representative able to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving any other investigational agents&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to melphalan&#xD;
&#xD;
          -  Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, uncontrolled hypertension (systolic &gt; 160, diastolic &gt; 100 despite&#xD;
             antihypertensive therapy, symptomatic congestive heart failure, unstable angina&#xD;
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would&#xD;
             limit compliance with study requirements&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients are excluded due to increased&#xD;
             risk of lethal infections when treated with myeloablative chemotherapy&#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>Samer S Srour</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>June 20, 2023</last_update_submitted>
  <last_update_submitted_qc>June 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Leukemia, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Nitrogen Mustard Compounds</mesh_term>
    <mesh_term>Elotuzumab</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/NCT01729091
org study id: 2011-0379
secondary id: NCI-2014-01096
secondary id: RV-MM-PI-0691
secondary id: NCI-2014-00541
secondary id: 2011-0379
nct id: NCT01729091
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies the side effects and best dose of umbilical cord blood-derived
      natural killer cells when given together with elotuzumab, lenalidomide, and high dose
      melphalan before autologous stem cell transplant and to see how well they work in treating
      patients with multiple myeloma. Before transplant, stem cells are taken from patients and
      stored. Immunotherapy with monoclonal antibodies, such as elotuzumab, may induce changes in
      the body's immune system and may interfere with the ability of cancer cells to grow and
      spread. Drugs used in chemotherapy, such as lenalidomide and melphalan, may 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. Giving chemotherapy before a stem cell
      transplant stops the growth of cancer cells by stopping them from dividing or killing them.
      Giving natural killer cells from donor umbilical cord blood before transplant may also kill
      myeloma cells that remain in the body after the last chemotherapy treatment. After treatment,
      stem cells are then returned to the patient to replace the blood-forming cells that were
      destroyed by the chemotherapy.
PRIMARY OBJECTIVES:

      I. To find the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived natural
      killer (NK) cells.

      II. To determine efficacy by the percent of patients achieving very good partial remission
      (VGPR) + complete remission (CR) at 3 months post-transplant.

      III. To assess the minimal residual disease rate 100 days post-transplant in high-risk
      patients.

      SECONDARY OBJECTIVE:

      I. To quantify duration of infused allogeneic donor UCB-derived NK cells in the recipient.

      OUTLINE: This is a dose-escalation study of UCB-derived NK cells.

      Patients receive elotuzumab intravenously (IV) over 2-5 hours on day -15 and -8, lenalidomide
      orally (PO) once daily (QD) on days -8 to -2, high-dose melphalan IV over 30 minutes on day
      -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell
      transplant on day 0.

      After completion of study treatment, patients are followed up at 30, 60 and 100 days and 6
      and 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells
time frame: Within 30 days post-transplant
description: Defined as the highest dose for which the probability of toxicity is closest to 20%. Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).
measure: Percent of patients achieving very good partial response (VGPR) + complete response (CR)
time frame: At 3 months post-transplant
description: Response will be tabulated by dose. Logistic regression methods will be used to model the rate of VGPR + CR as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities). Will estimate with a 95 percent credible interval.
measure: Minimal residual disease (MRD) rate
time frame: At 100 days
description: Will model the MRD rate in high-risk patients using logistical regression.
measure: Overall survival (OS)
time frame: Up to 12 months
description: OS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model OS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
measure: Progression-free survival (PFS)
time frame: Up to 12 months
description: PFS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model PFS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
measure: Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host
time frame: Up to 12 months
description: Will be reported as an average time value with standard deviation. These data may also be used as covariates in the regression models.
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
arm group type: Experimental
description: Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
intervention type: Procedure
intervention name: Autologous Hematopoietic Stem Cell Transplantation
description: Undergo autologous stem cell transplant
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
other name: Autologous Hematopoietic Cell Transplantation
other name: autologous stem cell transplantation
intervention type: Biological
intervention name: Elotuzumab
description: Given IV
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
other name: BMS-901608
other name: Empliciti
other name: HuLuc-63
other name: HuLuc63
other name: PDL-063
other name: PDL063
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Drug
intervention name: Melphalan
description: Given IV
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
other name: Alanine Nitrogen Mustard
other name: CB-3025
other name: L-PAM
other name: L-Phenylalanine Mustard
other name: L-sarcolysin
other name: L-Sarcolysin Phenylalanine mustard
other name: L-Sarcolysine
other name: Melphalanum
other name: Phenylalanine Mustard
other name: Phenylalanine nitrogen mustard
other name: Sarcoclorin
other name: Sarkolysin
other name: WR-19813
intervention type: Biological
intervention name: Natural Killer Cell Therapy
description: Given IV
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
intervention type: Biological
intervention name: Umbilical Cord Blood-Derived Lymphocyte Therapy
description: Given IV
arm group label: Treatment (chemotherapy, UCB-derived NK cells, transplant)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Samer S Srour
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Leukemia, Plasma Cell
mesh term: Lenalidomide
mesh term: Melphalan
mesh term: Mechlorethamine
mesh term: Nitrogen Mustard Compounds
mesh term: Elotuzumab