<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/NCT03267888</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00097324</org_study_id>
    <secondary_id>NCI-2017-01485</secondary_id>
    <secondary_id>RAD4106-17</secondary_id>
    <secondary_id>P30CA138292</secondary_id>
    <nct_id>NCT03267888</nct_id>
  </id_info>
  <brief_title>Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies the side effects of pembrolizumab and radiation therapy in&#xD;
      treating patients with stage I-III multiple myeloma that has come back after a period of&#xD;
      improvement or that does not respond to treatment. Monoclonal antibodies, such as&#xD;
      pembrolizumab, may block cancer growth in different ways by targeting certain cells.&#xD;
      Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving&#xD;
      pembrolizumab and radiation therapy may work better in treating patients with stage I-III&#xD;
      multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the safety of concurrent single/low dose radiation therapy (radiotherapy) (8&#xD;
      Gy/1fx) in combination with pembrolizumab in relapsed or refractory myeloma patients.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To characterize late toxicity (Common Terminology Criteria for Adverse Events [CTCAE] &gt;&#xD;
      grade 2 toxicity at 6 and 12 months) and the effect of radiation in combination with&#xD;
      pembrolizumab on systemic response rates using international myeloma working group (IMWG)&#xD;
      uniform response criteria for multiple myeloma at 6 months and 12 months.&#xD;
&#xD;
      II. To assess changes in positron emission tomography/computed tomography (PET/CT) as a&#xD;
      result of combining pembrolizumab and radiotherapy at 6 months and 12 months.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab&#xD;
      intravenously (IV) over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3&#xD;
      weeks for 2 years in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and then every 12&#xD;
      weeks thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 29, 2018</start_date>
  <completion_date type="Anticipated">September 20, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 20, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Incidence of adverse events</measure>
    <time_frame>Up to 12 months after study start</time_frame>
    <description>Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events. Proportion adverse events will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients achieving any response</measure>
    <time_frame>Up to 12 months after study start</time_frame>
    <description>According to International Myeloma Working Group (IMWG) criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response based on baseline changes on positron emission to positron emission tomography/computed tomography</measure>
    <time_frame>Up to 12 months after study start</time_frame>
    <description>Will be defined using International IMWG criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From first treatment on course 1, day 1 to the earlier of date of death and/or last follow up, assessed up to 12 months</time_frame>
    <description>Will be estimated using the Kaplan-Meier product-limit method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>ISS Stage I Plasma Cell Myeloma</condition>
  <condition>ISS Stage II Plasma Cell Myeloma</condition>
  <condition>ISS Stage III Plasma Cell Myeloma</condition>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Refractory Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Radiation therapy, pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab IV over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given 200 mg/kg IV.</description>
    <arm_group_label>Radiation therapy, pembrolizumab</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>MK-3475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.</description>
    <arm_group_label>Radiation therapy, pembrolizumab</arm_group_label>
    <other_name>Radiotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  International Staging System (ISS) stage I-III multiple myeloma that has progressive,&#xD;
             relapsed, or refractory disease&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) 0-1&#xD;
&#xD;
          -  Relapsed and/or refractory myeloma; there is no minimum or maximum number of previous&#xD;
             therapies that a patient may have received previously before being put on the current&#xD;
             trial&#xD;
&#xD;
          -  ≥ 1 osseous and/or extra-osseous lesion that can be radiated&#xD;
&#xD;
          -  Candidate for pembrolizumab (as determined by physician, and adequate organ function)&#xD;
&#xD;
          -  Candidate for radiotherapy (as determined by treatment physician); these patients can&#xD;
             have symptomatic disease and/or asymptomatic disease; a minimum of one site of&#xD;
             radiation is required to any osseous and/or any extra-osseous disease; radiation to&#xD;
             any bony parts of the head and neck, skull, spine, ribs, and/or extremities are&#xD;
             allowed; radiation to any bony part for documented lytic disease is allowed; radiation&#xD;
             to any soft tissue plasmacytoma (including osseous and extra-osseous plasmacytoma) is&#xD;
             allowed; the only exclusion criteria for radiation, is central nervous system (CNS)&#xD;
             metastases&#xD;
&#xD;
          -  Measurable myeloma disease (urine protein &gt; 200 mg in 24 hours [hr] urine collection,&#xD;
             serum free light chain ratio &gt; 100 with an abnormal k/l ratio, serum M protein &gt; 0.5&#xD;
             g/dl); 12 of the 24 patients do not have to have measurable disease&#xD;
&#xD;
          -  Negative urine pregnancy test within 2 weeks for female subjects; female subjects of&#xD;
             childbearing potential should have a negative urine or serum pregnancy within 72 hours&#xD;
             prior to receiving the first dose of study medication; if the urine test is positive&#xD;
             or cannot be confirmed as negative, a serum pregnancy test will be required&#xD;
&#xD;
               -  Female subjects of childbearing potential should be willing to use 2 methods of&#xD;
                  birth control or be surgically sterile, or abstain from heterosexual activity for&#xD;
                  the course of the study through 120 days after the last dose of study medication;&#xD;
                  subjects of childbearing potential are those who have not been surgically&#xD;
                  sterilized or have not been free from menses for &gt; 1 year&#xD;
&#xD;
               -  Male subjects should agree to use an adequate method of contraception starting&#xD;
                  with the first dose of study therapy through 120 days after the last dose of&#xD;
                  study therapy&#xD;
&#xD;
               -  Abstinence is acceptable, if this is the usual life style and preferred&#xD;
                  contraception for the patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous anti-programmed cell death protein 1 (PD1) or anti-PD-L1&#xD;
&#xD;
          -  Solitary plasmacytoma&#xD;
&#xD;
          -  Smoldering (asymptomatic) multiple myeloma&#xD;
&#xD;
          -  Currently participating and receiving study therapy or has participated in a study of&#xD;
             an investigational agent and received study therapy or used an investigational device&#xD;
             within 4 weeks of the first dose of treatment&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency&#xD;
&#xD;
          -  Known history of active TB (Bacillus tuberculosis)&#xD;
&#xD;
          -  Hypersensitivity to pembrolizumab or any of its recipients&#xD;
&#xD;
          -  Known additional malignancy that is progressing or requires active treatment&#xD;
             (exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin)&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs)&#xD;
&#xD;
          -  Known history of, or any evidence of active, non-infectious pneumonitis&#xD;
&#xD;
          -  Active infection requiring systemic therapy&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or&#xD;
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is&#xD;
             detected)&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy; NOTE:&#xD;
             seasonal influenza vaccines for injection are generally inactivated flu vaccines and&#xD;
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live&#xD;
             attenuated vaccines, and are not allowed&#xD;
&#xD;
          -  Patients requiring radiation for CNS diseases are excluded (CNS defined as brain soft&#xD;
             tissue/intra parenchymal metastases within the gray and white matter of the brain&#xD;
             and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal&#xD;
             carcinomatous disease)&#xD;
&#xD;
          -  Has a history of allogeneic stem cell transplantation&#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>Mohammad K. Khan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Mohammad K. Khan</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>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>Pembrolizumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 5, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT03267888/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03267888
org study id: IRB00097324
secondary id: NCI-2017-01485
secondary id: RAD4106-17
secondary id: P30CA138292
nct id: NCT03267888
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This pilot clinical trial studies the side effects of pembrolizumab and radiation therapy in
      treating patients with stage I-III multiple myeloma that has come back after a period of
      improvement or that does not respond to treatment. Monoclonal antibodies, such as
      pembrolizumab, may block cancer growth in different ways by targeting certain cells.
      Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving
      pembrolizumab and radiation therapy may work better in treating patients with stage I-III
      multiple myeloma.
PRIMARY OBJECTIVE:

      I. To evaluate the safety of concurrent single/low dose radiation therapy (radiotherapy) (8
      Gy/1fx) in combination with pembrolizumab in relapsed or refractory myeloma patients.

      SECONDARY OBJECTIVES:

      I. To characterize late toxicity (Common Terminology Criteria for Adverse Events [CTCAE] >
      grade 2 toxicity at 6 and 12 months) and the effect of radiation in combination with
      pembrolizumab on systemic response rates using international myeloma working group (IMWG)
      uniform response criteria for multiple myeloma at 6 months and 12 months.

      II. To assess changes in positron emission tomography/computed tomography (PET/CT) as a
      result of combining pembrolizumab and radiotherapy at 6 months and 12 months.

      OUTLINE:

      Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab
      intravenously (IV) over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3
      weeks for 2 years in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 12
      weeks thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: Up to 12 months after study start
description: Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events. Proportion adverse events will be reported.
measure: Number of patients achieving any response
time frame: Up to 12 months after study start
description: According to International Myeloma Working Group (IMWG) criteria.
measure: Overall response based on baseline changes on positron emission to positron emission tomography/computed tomography
time frame: Up to 12 months after study start
description: Will be defined using International IMWG criteria.
measure: Overall survival
time frame: From first treatment on course 1, day 1 to the earlier of date of death and/or last follow up, assessed up to 12 months
description: Will be estimated using the Kaplan-Meier product-limit method.
arm group label: Radiation therapy, pembrolizumab
arm group type: Experimental
description: Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab IV over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Pembrolizumab
description: Given 200 mg/kg IV.
arm group label: Radiation therapy, pembrolizumab
other name: Keytruda
other name: MK-3475
intervention type: Radiation
intervention name: Radiation Therapy
description: Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.
arm group label: Radiation therapy, pembrolizumab
other name: Radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohammad K. Khan, MD, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Mohammad K. Khan
investigator title: Principal Investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Pembrolizumab
provided document: 