<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/NCT03252600</url>
  </required_header>
  <id_info>
    <org_study_id>2016-200</org_study_id>
    <secondary_id>NCI-2017-01203</secondary_id>
    <secondary_id>2016-200</secondary_id>
    <secondary_id>P30CA022453</secondary_id>
    <nct_id>NCT03252600</nct_id>
  </id_info>
  <brief_title>Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis</brief_title>
  <official_title>A Randomized Phase 2 Trial of Lenalidomide/ Dexamethasone/ Elotuzumab +/- Cyclophosphamide Followed by Lenalidomide/ Dexamethasone/Elotuzumab Maintenance as Second-Line Therapy for Patients With Relapsed AL Amyloidosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barbara Ann Karmanos Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Multiple Myeloma Research Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Barbara Ann Karmanos Cancer Institute</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 randomized phase II trial studies how well lenalidomide, dexamethasone, and eotuzumab&#xD;
      with or without cyclophosphamide work in treating patients with primary amyloidosis that has&#xD;
      come back after a period of improvement. Drugs used in chemotherapy, such as lenalidomide,&#xD;
      dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Monoclonal antibodies, such as eotuzumab, may interfere with the ability of cancer&#xD;
      cells to grow and spread. Giving lenalidomide, dexamethasone, and eotuzumab with&#xD;
      cyclophosphamide may work better in treating patients with primary amyloidosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the rate of hematologic response of very good partial response (VGPR) or better&#xD;
      according to the International Society of Amyloidosis (ISA) hematologic response criteria.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess duration of hematologic response. II. To assess time to hematologic progression.&#xD;
      III. To assess overall hematologic response rate. IV. To assess complete hematologic response&#xD;
      rate. V. To assess organ response (according to ISA organ response criteria). VI. To assess&#xD;
      overall survival (OS).&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone intravenously&#xD;
      (IV) on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8,&#xD;
      15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats&#xD;
      every 28 days for up to 6 courses in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      ARM II: Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients&#xD;
      also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up&#xD;
      to 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      MAINTENANCE THERAPY: All patients receive lenalidomide PO on days 1-21 and dexamethasone IV&#xD;
      on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses&#xD;
      repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 25, 2017</start_date>
  <completion_date type="Anticipated">December 7, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 7, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major hematologic response (&gt;= very good partial response), or better</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be expressed as a proportion with Clopper-Pearson exact 95% confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibody parameters</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hematologic response</measure>
    <time_frame>The time from the first date a hematologic response is documented to the date of the first documented hematologic progression assessed up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ response</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be assessed by the investigator and reported in the electronic case report form and reported with descriptive statistics including 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to hematologic progression</measure>
    <time_frame>The time from the first date of first dose to the date of the first documented hematologic progression assessed up to 24 months</time_frame>
    <description>Will be reported with descriptive statistics including 95% confidence intervals.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">53</enrollment>
  <condition>Recurrent Primary Amyloidosis</condition>
  <arm_group>
    <arm_group_label>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8, 15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</arm_group_label>
    <other_name>Aacidexam</other_name>
    <other_name>Adexone</other_name>
    <other_name>Aknichthol Dexa</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Alin</other_name>
    <other_name>Alin Depot</other_name>
    <other_name>Alin Oftalmico</other_name>
    <other_name>Amplidermis</other_name>
    <other_name>Anemul mono</other_name>
    <other_name>Auricularum</other_name>
    <other_name>Auxiloson</other_name>
    <other_name>Baycuten</other_name>
    <other_name>Baycuten N</other_name>
    <other_name>Cortidexason</other_name>
    <other_name>Cortisumman</other_name>
    <other_name>Decacort</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decalix</other_name>
    <other_name>Decameth</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Dectancyl</other_name>
    <other_name>Dekacort</other_name>
    <other_name>Deltafluorene</other_name>
    <other_name>Deronil</other_name>
    <other_name>Desamethasone</other_name>
    <other_name>Desameton</other_name>
    <other_name>Dexa-Mamallet</other_name>
    <other_name>Dexa-Rhinosan</other_name>
    <other_name>Dexa-Scheroson</other_name>
    <other_name>Dexa-sine</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Dexacortin</other_name>
    <other_name>Dexafarma</other_name>
    <other_name>Dexafluorene</other_name>
    <other_name>Dexalocal</other_name>
    <other_name>Dexamecortin</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dexamethasonum</other_name>
    <other_name>Dexamonozon</other_name>
    <other_name>Dexapos</other_name>
    <other_name>Dexinoral</other_name>
    <other_name>Dexone</other_name>
    <other_name>Dinormon</other_name>
    <other_name>Fluorodelta</other_name>
    <other_name>Fortecortin</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadecadrol</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Lokalison-F</other_name>
    <other_name>Loverine</other_name>
    <other_name>Methylfluorprednisolone</other_name>
    <other_name>Millicorten</other_name>
    <other_name>Mymethasone</other_name>
    <other_name>Orgadrone</other_name>
    <other_name>Spersadex</other_name>
    <other_name>Visumetazone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</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>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</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>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (lenalidomide, dexamethasone, elotuzumab)</arm_group_label>
    <arm_group_label>Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy-proven histochemical diagnosis of amyloid light-chain (AL) amyloidosis based on&#xD;
             tissue specimens with Congo red staining or other histologic stain; thioflavin T or S,&#xD;
             or crystal violet; tandem mass spec or immunohistochemistry (IHC) confirmation of&#xD;
             immunoglobulin-derived amyloidosis is encouraged; cases in which histochemical&#xD;
             confirmation is lacking need to be discussed with one of the Multiple Myeloma Research&#xD;
             Foundation (MMRF) protocol chair/co-chairs&#xD;
&#xD;
          -  One prior line of therapy (defined as either one non-transplant regimen such as&#xD;
             MelDex, Vel-Dex or CyBorD, one autologous stem cell transplant, or one regimen of&#xD;
             non-transplant induction therapy followed by a single autologous stem cell transplant&#xD;
             (without hematologic progression between induction and autologous stem cell transplant&#xD;
             [ASCT])&#xD;
&#xD;
          -  Measurable hematologic disease as defined by:&#xD;
&#xD;
               -  Serum differential free light chain concentration (dFLC, difference between&#xD;
                  amyloid forming [involved] and non-amyloid forming [uninvolved] free light chain&#xD;
                  [FLC]) &gt;= 50 mg/L)&#xD;
&#xD;
          -  Objective measurable (cardiac, renal or liver) organ amyloid involvement defined as&#xD;
             follows (amyloid involvement of at least 1 required):&#xD;
&#xD;
               -  Mean wall thickness &gt; 12 mm on echocardiogram, with no other cardiac cause or an&#xD;
                  elevated NT-ProBNP (&gt; 332 ng/L) in the absence of renal failure or atrial&#xD;
                  fibrillation&#xD;
&#xD;
               -  Renal involvement is defined as proteinuria (predominantly albumin) &gt; 0.5 g/day&#xD;
                  in a 24-hour urine collection&#xD;
&#xD;
               -  Total liver span &gt; 15 cm in the absence of heart failure or alkaline phosphatase&#xD;
                  &gt; 1.5 times institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  NOTE: Amyloid involvement of other organ systems is allowed, but not required&#xD;
&#xD;
          -  Life expectancy of &gt;= 6 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  . Female subjects who are of non-reproductive potential (i.e., post-menopausal by&#xD;
             history for at least 24 consecutive months; OR history of hysterectomy; OR history of&#xD;
             bilateral tubal ligation; OR history of bilateral oophorectomy).Female of child&#xD;
             bearing potential (FCBP) must have a negative serum or urine pregnancy test with a&#xD;
             sensitivity of at least 25 mIU/mL or equivalent units of human chorionic gonadotropin&#xD;
             (hCG) within 10 ? 14 days prior to and again within 24 hours of starting lenalidomide&#xD;
             and study drug and must either commit to continue abstinence from heterosexual&#xD;
             intercourse or begin TWO acceptable methods of birth control, one highly effective&#xD;
             method and one additional effective method AT THE SAME TIME, at least 4 weeks before&#xD;
             she starts taking lenalidomide through 4 weeks after the last dose of lenalidomide and&#xD;
             5 half-lives after elotuzumab plus 30 days (duration of ovulatory cycle) for a total&#xD;
             of 180 days post-last dose of elotuzumab; FCBP must also agree to ongoing pregnancy&#xD;
             testing during the entire duration of treatment. Males must agree to use a latex or&#xD;
             synthetic condom during sexual contact with a FCBP even if they have had a vasectomy&#xD;
             from the time of signing the informed consent form through 28 days after the last dose&#xD;
             of lenalidomide and 5 half-lives of elotuzumab plus 90 days (duration of sperm&#xD;
             turnover) for a total of 180 days post-last dose of elotuzumab; these same patients&#xD;
             must not donate sperm; all patients must be counseled at a minimum of every 28 days&#xD;
             about pregnancy precautions and risks of fetal exposure; all patients prior to taking&#xD;
             lenalidomide, must be registered in and must comply with all requirements of the&#xD;
             lenalidomide Risk Evaluation and Mitigation Strategies (REMS) program&#xD;
&#xD;
          -  Ability to understand the purpose and risks of the study and provide signed and dated&#xD;
             informed consent and authorization to use protected health information&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,000 cells/mm^3 (1.0 x 10^9/L)&#xD;
&#xD;
          -  Platelet count &gt;= 75,000 cells/mm^3 (75 x 10^9/L)&#xD;
&#xD;
          -  Hemoglobin &gt;= 8.0 g/dl (red blood cell [RBC] transfusions are permitted)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN (except if the patient has Gilbert?s syndrome who can&#xD;
             have total bilirubin =&lt; 2 x ULN)&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 5 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 3.0&#xD;
             x ULN&#xD;
&#xD;
          -  Renal function: creatinine clearance by Cockcroft-Gault formula &gt;= 30 mL/min&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL&#xD;
             amyloidosis; exception: patients with amyloid heavy (AH) or mixed AL/AH type&#xD;
             amyloidosis are potentially eligible&#xD;
&#xD;
          -  Peripheral neuropathy &gt;= grade 3 sensory neuropathy or &gt;= grade 2 sensory neuropathy&#xD;
             with pain within 14 days of registration; prior neuropathy of this severity improved&#xD;
             due to medical management such as gabapentin are potentially eligible&#xD;
&#xD;
          -  Cardiac stage 2 or 3 with N-terminal prohormone (NT-pro)-B-type natriuretic peptide&#xD;
             (BNP) &gt; 8500 ng/L&#xD;
&#xD;
          -  Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA)&#xD;
             class 3 or 4 congestive heart failure, myocardial infarction within the previous 6&#xD;
             months, unstable angina pectoris, uncontrolled hypertension (defined as an average&#xD;
             systolic blood pressure [SBP] over 140 or a diastolic blood pressure [DBP] over 90&#xD;
             despite antihypertensive agents), clinically significant repetitive ventricular&#xD;
             arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or&#xD;
             clinically important autonomic disease; prior to study entry, any electrocardiogram&#xD;
             (ECG) abnormality at screening has to be documented by the investigator as not&#xD;
             medically relevant; NOTE: there is no lower limit of left ventricular ejection&#xD;
             fraction below which patients are excluded from participation&#xD;
&#xD;
          -  Any medical conditions that, in the investigator?s opinion, would impose excessive&#xD;
             risk to the patient or would adversely affect his/her participating in this study,&#xD;
             including:&#xD;
&#xD;
          -  Known active infection requiring parenteral anti-infective treatment at the time of&#xD;
             initiation of treatment&#xD;
&#xD;
          -  Other malignancy diagnosed or requiring treatment within the past 3 years with the&#xD;
             exception of adequately treated basal cell carcinoma, squamous cell skin cancer,&#xD;
             carcinoma in-situ of the cervix or breast, or low-risk Gleason grade =&lt; 6 localized&#xD;
             prostate cancer not requiring therapy&#xD;
&#xD;
          -  Pregnant or breast-feeding females&#xD;
&#xD;
          -  Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or&#xD;
             confuse compliance or follow-up evaluation&#xD;
&#xD;
          -  Known or active human immunodeficiency virus (HIV) infection or active hepatitis B or&#xD;
             C viral infection&#xD;
&#xD;
          -  Cerebrovascular accident (CVA) with persistent neurologic deficits occurring within 6&#xD;
             months prior to enrollment; persisting neurologic deficits from a CVA occurring over 6&#xD;
             months prior to enrollment are not necessarily grounds for exclusion&#xD;
&#xD;
          -  Concurrent multiple myeloma (defined according to 2015 International Myeloma Working&#xD;
             Group [IMWG] guidelines)&#xD;
&#xD;
          -  POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein [M-protein] and skin changes)&#xD;
&#xD;
          -  Previous cytotoxic therapies, including cytotoxic investigational agents, within 3&#xD;
             weeks (6 weeks nitrosoureas) prior to start of study treatment; previous&#xD;
             corticosteroids used with intent to treat amyloidosis within three weeks; (prednisone&#xD;
             up to but no more than 10 mg orally once a day [q.d.] or its equivalent for symptom&#xD;
             management of comorbid conditions is permitted but dose should be stable for at least&#xD;
             7 days prior to study treatment)&#xD;
&#xD;
          -  Residual side effects to previous therapy &gt; grade 1 prior to initiation of therapy&#xD;
             (alopecia any grade and/or neuropathy grade 2 without pain are permitted)&#xD;
&#xD;
          -  Prior autologous or allogeneic stem cell transplant within 12 weeks of initiation of&#xD;
             therapy&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant within 16 weeks of initiation of therapy, or at&#xD;
             any time if patient has active graft-versus-host-disease (GVHD)&#xD;
&#xD;
          -  Prior major surgical procedure or radiation therapy within 4 weeks of the first dose&#xD;
             of study treatment (this does not include limited course of radiation used for&#xD;
             management of bone pain within 7 days of first dose of study therapy)&#xD;
&#xD;
          -  Known intolerance to steroid therapy (defined as being unable to tolerate at least 20&#xD;
             mg dex/week)&#xD;
&#xD;
          -  Inability to tolerate prophylactic anti-thrombotic therapy&#xD;
&#xD;
          -  &gt;= grade 3 thromboembolic event in the last 6 months&#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>Jeffrey Zonder, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barbara Ann Karmanos Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>January 20, 2023</last_update_submitted>
  <last_update_submitted_qc>January 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Barbara Ann Karmanos Cancer Institute</investigator_affiliation>
    <investigator_full_name>Jeffrey Zonder</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin Light-chain Amyloidosis</mesh_term>
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Elotuzumab</mesh_term>
    <mesh_term>Ichthammol</mesh_term>
    <mesh_term>BB 1101</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/NCT03252600
org study id: 2016-200
secondary id: NCI-2017-01203
secondary id: 2016-200
secondary id: P30CA022453
nct id: NCT03252600
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II trial studies how well lenalidomide, dexamethasone, and eotuzumab
      with or without cyclophosphamide work in treating patients with primary amyloidosis that has
      come back after a period of improvement. Drugs used in chemotherapy, such as lenalidomide,
      dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Monoclonal antibodies, such as eotuzumab, may interfere with the ability of cancer
      cells to grow and spread. Giving lenalidomide, dexamethasone, and eotuzumab with
      cyclophosphamide may work better in treating patients with primary amyloidosis.
PRIMARY OBJECTIVES:

      I. To assess the rate of hematologic response of very good partial response (VGPR) or better
      according to the International Society of Amyloidosis (ISA) hematologic response criteria.

      SECONDARY OBJECTIVES:

      I. To assess duration of hematologic response. II. To assess time to hematologic progression.
      III. To assess overall hematologic response rate. IV. To assess complete hematologic response
      rate. V. To assess organ response (according to ISA organ response criteria). VI. To assess
      overall survival (OS).

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone intravenously
      (IV) on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8,
      15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats
      every 28 days for up to 6 courses in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients
      also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up
      to 6 courses in the absence of disease progression or unacceptable toxicity.

      MAINTENANCE THERAPY: All patients receive lenalidomide PO on days 1-21 and dexamethasone IV
      on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses
      repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months for 24 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major hematologic response (>= very good partial response), or better
time frame: Up to 24 months
description: Will be expressed as a proportion with Clopper-Pearson exact 95% confidence intervals.
measure: Anti-drug antibody parameters
time frame: Up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals.
measure: Complete response rate
time frame: Up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.
measure: Duration of hematologic response
time frame: The time from the first date a hematologic response is documented to the date of the first documented hematologic progression assessed up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.
measure: Organ response
time frame: Up to 24 months
description: Will be assessed by the investigator and reported in the electronic case report form and reported with descriptive statistics including 95% confidence intervals.
measure: Overall response rate
time frame: Up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.
measure: Overall survival
time frame: Up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.
measure: Time to hematologic progression
time frame: The time from the first date of first dose to the date of the first documented hematologic progression assessed up to 24 months
description: Will be reported with descriptive statistics including 95% confidence intervals.
arm group label: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group type: Experimental
description: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8, 15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
arm group type: Experimental
description: Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Dexamethasone
description: Given IV
arm group label: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
other name: Aacidexam
other name: Adexone
other name: Aknichthol Dexa
other name: Alba-Dex
other name: Alin
other name: Alin Depot
other name: Alin Oftalmico
other name: Amplidermis
other name: Anemul mono
other name: Auricularum
other name: Auxiloson
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decalix
other name: Decameth
other name: Decasone R.p.
other name: Dectancyl
other name: Dekacort
other name: Deltafluorene
other name: Deronil
other name: Desamethasone
other name: Desameton
other name: Dexa-Mamallet
other name: Dexa-Rhinosan
other name: Dexa-Scheroson
other name: Dexa-sine
other name: Dexacortal
other name: Dexacortin
other name: Dexafarma
other name: Dexafluorene
other name: Dexalocal
other name: Dexamecortin
other name: Dexameth
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Fluorodelta
other name: Fortecortin
other name: Gammacorten
other name: Hexadecadrol
other name: Hexadrol
other name: Lokalison-F
other name: Loverine
other name: Methylfluorprednisolone
other name: Millicorten
other name: Mymethasone
other name: Orgadrone
other name: Spersadex
other name: Visumetazone
intervention type: Biological
intervention name: Elotuzumab
description: Given IV
arm group label: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
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: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Arm I (lenalidomide, dexamethasone, elotuzumab)
arm group label: Arm II(lenalidomide,dexamethasone,elotuzumab,cyclophosphamide)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Zonder, M.D.
role: Principal Investigator
affiliation: Barbara Ann Karmanos Cancer Institute
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Barbara Ann Karmanos Cancer Institute
investigator full name: Jeffrey Zonder
investigator title: Principal Investigator
mesh term: Immunoglobulin Light-chain Amyloidosis
mesh term: Amyloidosis
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Cyclophosphamide
mesh term: Lenalidomide
mesh term: Elotuzumab
mesh term: Ichthammol
mesh term: BB 1101