<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/NCT01689987</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00008296</org_study_id>
    <secondary_id>NCI-2012-01754</secondary_id>
    <secondary_id>CR00022154</secondary_id>
    <secondary_id>MR00041096</secondary_id>
    <secondary_id>IRB00008296</secondary_id>
    <secondary_id>P30CA069533</secondary_id>
    <nct_id>NCT01689987</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine, Cyclophosphamide, Dexamethasone, and Sirolimus in Treating Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>A Phase I Dose Escalation Study of Hydroxychloroquine With Infusional Cyclophosphamide, Pulse Dexamethasone and Rapamycin in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of hydroxychloroquine when given&#xD;
      together with cyclophosphamide, dexamethasone, and sirolimus in treating patients with&#xD;
      multiple myeloma that has come back after a period of improvement or does not respond to&#xD;
      treatment. Biological therapies, such as hydroxychloroquine, may stimulate the immune system&#xD;
      in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer&#xD;
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,&#xD;
      such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of&#xD;
      cancer cells, either by killing the cells, stopping them from dividing, or by stopping them&#xD;
      from spreading. Giving hydroxychloroquine together with sirolimus, cyclophosphamide, and&#xD;
      dexamethasone may be a better treatment for multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination&#xD;
      with rapamycin (sirolimus) and infusional cyclophosphamide and pulse dexamethasone (cy/dex)&#xD;
      for patients with relapsed/ refractory multiple myeloma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate biological activity and efficacy of the combination of cyclophosphamide,&#xD;
      dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/refractory multiple&#xD;
      myeloma.&#xD;
&#xD;
      II. To determine whether this treatment regimen results in mammalian target of rapamycin&#xD;
      (mTOR) and autophagy inhibition in primary myeloma cells during therapy and if this&#xD;
      corresponds with treatment responses.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of hydroxychloroquine.&#xD;
&#xD;
      Patients receive hydroxychloroquine orally (PO) daily on days 1-28 (days 5-28 of course 1),&#xD;
      sirolimus PO on days -2 to 4, and cyclophosphamide intravenously (IV) continuously and&#xD;
      dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <primary_completion_date type="Actual">April 2016</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>MTD of hydroxychloroquine defined as the highest dose at which 0/6 or 1/6 subjects experience a dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0</measure>
    <time_frame>56 days</time_frame>
    <description>Incidence of DLTs will be tabulated for each dose level. Summarized using descriptive statistics or frequency distributions, as appropriate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of overall response</measure>
    <time_frame>Time that measurement criteria are met for response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 months</time_frame>
    <description>Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myeloma response (stringent complete response, complete response, very good partial response, partial response, stable disease, and progressive disease), as assessed by the International Myeloma Working Group</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Presented with two-sided 95% exact binomial confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 12 months</time_frame>
    <description>Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response</measure>
    <time_frame>Time from the first day of therapy until the time that measurement criteria are met for response, assessed up to 12 months</time_frame>
    <description>Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mean percentage of p70S6 myeloma cells</measure>
    <time_frame>Up to day 5 of course 2</time_frame>
    <description>The mean percentage of p70S6 myeloma cells and the number of autophagic vesicles per bone marrow plasma cells will be compared between responders and non-responders using two-sample test if the data follows normal distribution or if the data does not follow normal distribution, transformation or non-parametric method will be considered.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of autophagic vesicles per bone marrow plasma cells</measure>
    <time_frame>Up to day 5 of course 2</time_frame>
    <description>The mean percentage of p70S6 myeloma cells and the number of autophagic vesicles per bone marrow plasma cells will be compared between responders and non-responders using two-sample test if the data follows normal distribution or if the data does not follow normal distribution, transformation or non-parametric method will be considered.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Refractory Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive hydroxychloroquine PO daily on days 1-28 (days 5-28 of course 1), sirolimus PO on days -2 to 4, and cyclophosphamide IV continuously and dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses 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>Treatment (HCQ, sirolimus, cy/dex)</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 PO</description>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</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>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (HCQ, sirolimus, cy/dex)</arm_group_label>
    <other_name>AY 22989</other_name>
    <other_name>RAPA</other_name>
    <other_name>Rapamune</other_name>
    <other_name>RAPAMYCIN</other_name>
    <other_name>SILA 9268A</other_name>
    <other_name>WY-090217</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed multiple myeloma&#xD;
&#xD;
          -  Documented relapse or persistent disease after at least 1 prior therapy containing&#xD;
             both bortezomib and lenalidomide; or at least 2 prior therapies containing bortezomib&#xD;
             in one and lenalidomide in the other, or if intolerant of bortezomib and/or&#xD;
             lenalidomide; prior autologous and allogeneic bone marrow transplantation are allowed&#xD;
&#xD;
          -  Need for further treatment for myeloma, as determined by the patient's treating&#xD;
             physician; this is defined as progression of clinical features (worsening anemia,&#xD;
             renal function, bone disease, hypercalcemia, recurrent infections, and constitutional&#xD;
             symptoms) OR biochemical progression (increasing M-spike in serum or urine, involved&#xD;
             serum or urine free light chain over 2 consecutive time points greater than 4 weeks&#xD;
             apart)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Birth control is required with full barrier contraceptives or complete abstinence for&#xD;
             the duration of time receiving therapy and for 6 months after completing the last drug&#xD;
             taken&#xD;
&#xD;
          -  The need for further treatment: this is defined as progression of clinical features&#xD;
             (worsening anemia, renal function, bone disease, hypercalcemia, recurrent infections,&#xD;
             and constitutional symptoms) OR biochemical progression (increasing M-spike in serum&#xD;
             or urine, involved serum or urine free light chain over 2 consecutive time points&#xD;
             greater than 4 weeks apart)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions to compounds of similar chemical or biological&#xD;
             composition to rapamycin or hydroxychloroquine&#xD;
&#xD;
          -  Patients may not take any of the following medications while on study, but will be&#xD;
             considered eligible if medication is discontinued at least 72 hours (hrs) prior to&#xD;
             first dose of Rapamycin:&#xD;
&#xD;
               -  Carbamazepine&#xD;
&#xD;
               -  Rifabutin&#xD;
&#xD;
               -  Rifampin&#xD;
&#xD;
               -  Rifapentine&#xD;
&#xD;
               -  St. John's wort&#xD;
&#xD;
               -  Clarithromycin&#xD;
&#xD;
               -  Cyclosporine&#xD;
&#xD;
               -  Diltiazem&#xD;
&#xD;
               -  Erythromycin&#xD;
&#xD;
               -  Itraconazole&#xD;
&#xD;
               -  Fluconazole&#xD;
&#xD;
               -  Ketoconazole&#xD;
&#xD;
               -  Telithromycin&#xD;
&#xD;
               -  Verapamil&#xD;
&#xD;
               -  Voriconazole&#xD;
&#xD;
               -  Posaconazole&#xD;
&#xD;
          -  Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or&#xD;
             psoriasis (well-controlled psoriasis allowed provided under the care of a specialist&#xD;
             who agrees to monitor the patient for exacerbations)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) =&lt; 1.0 x 10^9/L&#xD;
&#xD;
          -  Platelets =&lt; 50 x 10^9/L for any reason&#xD;
&#xD;
          -  Serum creatinine &gt;= 2.5 mg/dL&#xD;
&#xD;
          -  Total or direct bilirubin &gt;= 2.0 mg/dL&#xD;
&#xD;
          -  Transaminases 2 x the upper limit of normal&#xD;
&#xD;
          -  Fasting glucose &gt;= 200 mg/dL&#xD;
&#xD;
          -  Serum potassium &lt; 3.4 mmol/l&#xD;
&#xD;
          -  Serum phosphorus &lt; 2.4 mg/dl&#xD;
&#xD;
          -  Other conditions that would require therapy with hydroxychloroquine, including but not&#xD;
             limited to, any of the following:&#xD;
&#xD;
               -  Systemic lupus&#xD;
&#xD;
               -  Rheumatoid arthritis&#xD;
&#xD;
               -  Porphyria cutanea tarda&#xD;
&#xD;
               -  Malaria treatment or prophylaxis&#xD;
&#xD;
          -  Evidence of other active malignancy, except:&#xD;
&#xD;
               -  Basal cell or squamous cell carcinoma of the skin&#xD;
&#xD;
               -  Treated carcinoma in situ&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, any of the following:&#xD;
&#xD;
               -  Uncontrolled ongoing infection&#xD;
&#xD;
               -  Human immunodeficiency virus (HIV)&#xD;
&#xD;
               -  Hepatitis B infection&#xD;
&#xD;
               -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency&#xD;
&#xD;
               -  Symptomatic congestive heart failure&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
               -  Uncontrolled cardiac arrhythmia&#xD;
&#xD;
               -  Psychiatric illness or social situations that would limit compliance with study&#xD;
                  requirements&#xD;
&#xD;
               -  Active graft-versus-host disease (GvHD)&#xD;
&#xD;
          -  Inability to understand or unwillingness to sign the informed consent document&#xD;
&#xD;
          -  Concurrent anti-myeloma therapy within:&#xD;
&#xD;
               -  7 days of prior corticosteroids&#xD;
&#xD;
               -  14 days of prior antimyeloma agents, including thalidomide or lenalidomide&#xD;
&#xD;
               -  28 days of a different investigational regimen&#xD;
&#xD;
               -  14 days of any radiation&#xD;
&#xD;
          -  Women of child-bearing who are unwilling or unable to use an acceptable method to&#xD;
             avoid pregnancy for the entire study period and for up to 30 days after the last dose&#xD;
             of study drug&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  History of G6PD deficiency&#xD;
&#xD;
          -  Known history of HIV infection&#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>Emma Scott</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>September 5, 2017</last_update_submitted>
  <last_update_submitted_qc>September 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Emma Scott</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Cyclophosphamide</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/NCT01689987
org study id: IRB00008296
secondary id: NCI-2012-01754
secondary id: CR00022154
secondary id: MR00041096
secondary id: IRB00008296
secondary id: P30CA069533
nct id: NCT01689987
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and best dose of hydroxychloroquine when given
      together with cyclophosphamide, dexamethasone, and sirolimus in treating patients with
      multiple myeloma that has come back after a period of improvement or does not respond to
      treatment. Biological therapies, such as hydroxychloroquine, may stimulate the immune system
      in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,
      such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of
      cancer cells, either by killing the cells, stopping them from dividing, or by stopping them
      from spreading. Giving hydroxychloroquine together with sirolimus, cyclophosphamide, and
      dexamethasone may be a better treatment for multiple myeloma.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination
      with rapamycin (sirolimus) and infusional cyclophosphamide and pulse dexamethasone (cy/dex)
      for patients with relapsed/ refractory multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate biological activity and efficacy of the combination of cyclophosphamide,
      dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/refractory multiple
      myeloma.

      II. To determine whether this treatment regimen results in mammalian target of rapamycin
      (mTOR) and autophagy inhibition in primary myeloma cells during therapy and if this
      corresponds with treatment responses.

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

      Patients receive hydroxychloroquine orally (PO) daily on days 1-28 (days 5-28 of course 1),
      sirolimus PO on days -2 to 4, and cyclophosphamide intravenously (IV) continuously and
      dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD of hydroxychloroquine defined as the highest dose at which 0/6 or 1/6 subjects experience a dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0
time frame: 56 days
description: Incidence of DLTs will be tabulated for each dose level. Summarized using descriptive statistics or frequency distributions, as appropriate.
measure: Duration of overall response
time frame: Time that measurement criteria are met for response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 months
description: Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.
measure: Myeloma response (stringent complete response, complete response, very good partial response, partial response, stable disease, and progressive disease), as assessed by the International Myeloma Working Group
time frame: Up to 12 months
description: Presented with two-sided 95% exact binomial confidence interval.
measure: Progression-free survival
time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 12 months
description: Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.
measure: Time to response
time frame: Time from the first day of therapy until the time that measurement criteria are met for response, assessed up to 12 months
description: Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.
measure: Mean percentage of p70S6 myeloma cells
time frame: Up to day 5 of course 2
description: The mean percentage of p70S6 myeloma cells and the number of autophagic vesicles per bone marrow plasma cells will be compared between responders and non-responders using two-sample test if the data follows normal distribution or if the data does not follow normal distribution, transformation or non-parametric method will be considered.
measure: Number of autophagic vesicles per bone marrow plasma cells
time frame: Up to day 5 of course 2
description: The mean percentage of p70S6 myeloma cells and the number of autophagic vesicles per bone marrow plasma cells will be compared between responders and non-responders using two-sample test if the data follows normal distribution or if the data does not follow normal distribution, transformation or non-parametric method will be considered.
arm group label: Treatment (HCQ, sirolimus, cy/dex)
arm group type: Experimental
description: Patients receive hydroxychloroquine PO daily on days 1-28 (days 5-28 of course 1), sirolimus PO on days -2 to 4, and cyclophosphamide IV continuously and dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (HCQ, sirolimus, cy/dex)
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 PO
arm group label: Treatment (HCQ, sirolimus, cy/dex)
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: Drug
intervention name: Hydroxychloroquine
description: Given PO
arm group label: Treatment (HCQ, sirolimus, cy/dex)
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (HCQ, sirolimus, cy/dex)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (HCQ, sirolimus, cy/dex)
intervention type: Drug
intervention name: Sirolimus
description: Given PO
arm group label: Treatment (HCQ, sirolimus, cy/dex)
other name: AY 22989
other name: RAPA
other name: Rapamune
other name: RAPAMYCIN
other name: SILA 9268A
other name: WY-090217
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emma Scott
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Emma Scott
investigator title: Assistant Professor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Sirolimus
mesh term: Hydroxychloroquine
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Cyclophosphamide
mesh term: Ichthammol
mesh term: BB 1101