<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/NCT04466475</url>
  </required_header>
  <id_info>
    <org_study_id>RG1006317</org_study_id>
    <secondary_id>NCI-2019-06979</secondary_id>
    <secondary_id>10306</secondary_id>
    <secondary_id>R01CA205248</secondary_id>
    <nct_id>NCT04466475</nct_id>
  </id_info>
  <brief_title>Radioimmunotherapy (211At-OKT10-B10) and Chemotherapy (Melphalan) Before Stem Cell Transplantation for the Treatment of Multiple Myeloma</brief_title>
  <official_title>A Phase I Trial Evaluating Escalating Doses of 211At-Labeled Anti-CD38 Monoclonal Antibody (211At-OKT10-B10) Combined With Melphalan as Conditioning Prior to Autologous Hematopoietic Cell Transplantation for Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <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>Fred Hutchinson Cancer Center</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 phase I trial studies the side effects and best dose of 211At-OKT10-B10 when given&#xD;
      together with melphalan before a stem cell transplantation in treating patients with multiple&#xD;
      myeloma. The radioimmunotherapy drug 211At-OKT10-B10 is a monoclonal antibody, called&#xD;
      OKT10-B10, linked to a radioactive substance called 211At. OKT10-B10 attaches to CD38&#xD;
      positive cancer cells in a targeted way and delivers 211At to kill them. Drugs used in&#xD;
      chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells,&#xD;
      either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving 211At-OKT10-B10 with melphalan before a stem cell transplant may kill more&#xD;
      cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE: This is a dose-escalation study of 211At-OKT10-B10.&#xD;
&#xD;
      Patients receive 211At-OKT10-B10 intravenously (IV) continuously on day -10 to day - 4&#xD;
      (approximately day -7) and melphalan via infusion on day -2. Patients then undergo&#xD;
      hematopoietic cell transplantation (HCT) on day 0.&#xD;
&#xD;
      After completion of study treatment, patients are followed for 30 days, between 80 and 90&#xD;
      days, at 6, 9, 12, 18, and 24 months, and then annually thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">October 13, 2023</start_date>
  <completion_date type="Anticipated">September 30, 2027</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2025</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>Maximum tolerated dose</measure>
    <time_frame>Up to 30 days post-transplant</time_frame>
    <description>Defined a true dose limiting toxicity (DLT) probability of 25% of subjects, where a DLT is defined as any grade 3-5 nonhematologic regimen-related toxicity within the first 30 days following autologous hematopoietic cell transplantation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Achievement of response</measure>
    <time_frame>Between days +80 to +90 post-transplant</time_frame>
    <description>Measured per the International Myeloma Working Group criteria. The response rates (partial response [PR] or better) will be estimated along with the exact 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>From response (PR or better) to disease relapse or death, assessed up to 5 years</time_frame>
    <description>Duration of response will be estimated using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From transplantation to death, assessed up to 2 years post-transplant</time_frame>
    <description>Kaplan-Meier methodology will be used to estimate the 2-year overall survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>From transplantation to disease relapse or death, assessed up to 2 years post-transplant</time_frame>
    <description>Kaplan-Meier methodology will be used to estimate the 2-year progression-free survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of minimal residual disease (MRD)</measure>
    <time_frame>At days 28, and +80 to +90 post-transplant</time_frame>
    <description>MRD will be assessed using multi-color flow cytometry and next generation sequencing in conjunction with functional imaging (i.e., positron emission tomography-computed tomography). The proportion who achieve MRD will be estimated along with an exact 95% confidence interval.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive 211At-OKT10-B10 IV continuously on day -10 to day - 4 (approximately day -7) and melphalan via infusion on day -2. Patients then undergo HCT on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)</arm_group_label>
    <other_name>211At-OKT10-B10</other_name>
    <other_name>[211At]OKT10-B10</other_name>
    <other_name>Astatine 211-labeled Anti-CD38 Monoclonal Antibody OKT10-B10</other_name>
    <other_name>Astatine At 211 Anti-CD38 MoAb OKT10-B10</other_name>
    <other_name>Astatine-211-OKT10-B10</other_name>
    <other_name>At211-OKT10-B10</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given via infusion</description>
    <arm_group_label>Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)</arm_group_label>
    <other_name>Alanine Nitrogen Mustard</other_name>
    <other_name>CB-3025</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-Phenylalanine Mustard</other_name>
    <other_name>L-Sarcolysin</other_name>
    <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysine</other_name>
    <other_name>Melphalanum</other_name>
    <other_name>Phenylalanine Mustard</other_name>
    <other_name>Phenylalanine Nitrogen Mustard</other_name>
    <other_name>Sarcoclorin</other_name>
    <other_name>Sarkolysin</other_name>
    <other_name>WR-19813</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo PBSC transplantation</description>
    <arm_group_label>Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)</arm_group_label>
    <other_name>PBPC transplantation</other_name>
    <other_name>PBSCT</other_name>
    <other_name>Peripheral Blood Progenitor Cell Transplantation</other_name>
    <other_name>Peripheral Stem Cell Support</other_name>
    <other_name>Peripheral Stem Cell Transplant</other_name>
    <other_name>Peripheral Stem Cell Transplantation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of multiple myeloma&#xD;
&#xD;
          -  Patients must have autologous hematopoietic stem cells collected with a minimum CD34+&#xD;
             stem cell yield of &gt;= 4 x 10^6 CD34+ cells/kg of body weight&#xD;
&#xD;
          -  Subjects must have disease meeting criteria for clinical relapse or progressive&#xD;
             disease (International Myeloma Working Group [IMWG] consensus criteria) and a history&#xD;
             of &gt;= 1 prior autologous stem cell transplant(s)&#xD;
&#xD;
          -  Subjects must have received at least 3 prior lines of therapy: an immunomodulatory&#xD;
             drug, a proteasome inhibitor, and a CD38-targeting antibody&#xD;
&#xD;
             * Aline of therapy is defined as one or more cycles of a planned treatment program.&#xD;
             This may consist of one or more planned cycles of a single-agent therapy or&#xD;
             combination therapy, as well as a sequence of treatments administered in a planned&#xD;
             manner. For example, a planned treatment approach of induction therapy followed by&#xD;
             autologous stem cell transplantation, followed by maintenance is considered one line&#xD;
             of therapy. A new line of therapy starts when a planned course of therapy is modified&#xD;
             to include other treatment agents (alone or in combination) as a results of disease&#xD;
             progression, relapse, or toxicity. A new line of therapy also starts when a planned&#xD;
             period of observation off therapy is interrupted by a need for additional treatment&#xD;
             for the disease&#xD;
&#xD;
          -  Subjects must have an estimated creatinine clearance greater than 60 ml per minute by&#xD;
             the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 +/-&#xD;
             days prior to registration&#xD;
&#xD;
          -  Subjects must have an Eastern Cooperative Oncology Group (ECOG) score =&lt; 2 or&#xD;
             Karnofsky score &gt;= 70%&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
          -  Subjects 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of plasma cell leukemia&#xD;
&#xD;
          -  History of central nervous system involvement by multiple myeloma&#xD;
&#xD;
          -  Prior radioimmunotherapy or radiation of &gt; 20 Gy to pelvis or at maximally tolerated&#xD;
             levels to any critical normal organ&#xD;
&#xD;
          -  Prior allogeneic hematopoietic cell transplant&#xD;
&#xD;
          -  More than 2 prior autologous hematopoietic cell transplants&#xD;
&#xD;
          -  Subjects with medullary or extramedullary plasmacytoma/s measuring &gt; 3 cm by magnetic&#xD;
             resonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT)&#xD;
             (radiated lesions are exempt from this criterion)&#xD;
&#xD;
          -  Subjects with a history of any one of the following cardiovascular conditions within&#xD;
             the past 6 months: Class III or IV heart failure as defined by the New York Heart&#xD;
             Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable&#xD;
             angina, or other clinically significant cardiac disease as determined by the principal&#xD;
             investigator (PI) or designee&#xD;
&#xD;
          -  Subjects with corrected QT (QTc) prolongation at baseline&#xD;
&#xD;
          -  Subjects with a history of cardiac arrhythmia and a heart rate &gt; 100 beats per minute&#xD;
             (BPM) (oral beta-blocker [excluding sotalol] and/or calcium channel blocker therapy&#xD;
             are acceptable to achieve rate control)&#xD;
&#xD;
          -  History of reactive airway disease and clinically significant asthma requiring any&#xD;
             form of medical treatment in the prior three months&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 40%&#xD;
&#xD;
          -  Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) &lt; 50% or&#xD;
             receiving supplemental continuous oxygen&#xD;
&#xD;
          -  Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of&#xD;
             portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy,&#xD;
             uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the&#xD;
             prothrombin time, ascites related to portal hypertension, bacterial or fungal liver&#xD;
             abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.&#xD;
&#xD;
          -  Bilirubin &gt; 2 times the upper limit of normal&#xD;
&#xD;
          -  Aspartate aminotransferase [AST] and alanine aminotransferase [ALT] &gt; 2 times the&#xD;
             upper limit of normal&#xD;
&#xD;
          -  Subjects who are known to be seropositive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin&#xD;
             [HCG]+) or breast feeding&#xD;
&#xD;
          -  Fertile subjects unwilling to use contraceptives during and for 12 months&#xD;
             post-transplant&#xD;
&#xD;
          -  Subjects with untreated and uncontrolled infection at time of enrollment&#xD;
&#xD;
          -  Subjects with known amyloid light-chain (AL) subtype amyloidosis&#xD;
&#xD;
          -  Known allergy to murine-based monoclonal antibodies&#xD;
&#xD;
          -  Known contraindications to radiotherapy&#xD;
&#xD;
          -  History of another primary malignancy that has not been in remission for at least 2&#xD;
             years (the following are exempt from the 2-year limit: non-melanoma skin cancer,&#xD;
             curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy&#xD;
             or a squamous intraepithelial lesion on Papanicolaou [PAP] smear)&#xD;
&#xD;
          -  Any anti-CD38 monoclonal antibody within 30 days of anticipated date of infusion of&#xD;
             211At-OKT10-B10&#xD;
&#xD;
          -  Individuals with a history of CTCAE grade 4 gastrointestinal toxicity associated with&#xD;
             prior high-dose melphalan conditioning therapy (previous autologous stem cell&#xD;
             transplant)&#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>Damian J. Green</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Damian J. Green</last_name>
    <phone>206-667-5398</phone>
    <email>dgreen@fredhutch.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Damian J. Green</last_name>
      <phone>206-667-5398</phone>
      <email>dgreen@fredhutch.org</email>
    </contact>
    <investigator>
      <last_name>Damian J. Green</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Nitrogen Mustard Compounds</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04466475
org study id: RG1006317
secondary id: NCI-2019-06979
secondary id: 10306
secondary id: R01CA205248
nct id: NCT04466475
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of 211At-OKT10-B10 when given
      together with melphalan before a stem cell transplantation in treating patients with multiple
      myeloma. The radioimmunotherapy drug 211At-OKT10-B10 is a monoclonal antibody, called
      OKT10-B10, linked to a radioactive substance called 211At. OKT10-B10 attaches to CD38
      positive cancer cells in a targeted way and delivers 211At to kill them. Drugs used in
      chemotherapy, such as melphalan, 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. Giving 211At-OKT10-B10 with melphalan before a stem cell transplant may kill more
      cancer cells.
OUTLINE: This is a dose-escalation study of 211At-OKT10-B10.

      Patients receive 211At-OKT10-B10 intravenously (IV) continuously on day -10 to day - 4
      (approximately day -7) and melphalan via infusion on day -2. Patients then undergo
      hematopoietic cell transplantation (HCT) on day 0.

      After completion of study treatment, patients are followed for 30 days, between 80 and 90
      days, at 6, 9, 12, 18, and 24 months, and then annually thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose
time frame: Up to 30 days post-transplant
description: Defined a true dose limiting toxicity (DLT) probability of 25% of subjects, where a DLT is defined as any grade 3-5 nonhematologic regimen-related toxicity within the first 30 days following autologous hematopoietic cell transplantation.
measure: Achievement of response
time frame: Between days +80 to +90 post-transplant
description: Measured per the International Myeloma Working Group criteria. The response rates (partial response [PR] or better) will be estimated along with the exact 95% confidence interval.
measure: Duration of response
time frame: From response (PR or better) to disease relapse or death, assessed up to 5 years
description: Duration of response will be estimated using Kaplan-Meier methodology.
measure: Overall survival
time frame: From transplantation to death, assessed up to 2 years post-transplant
description: Kaplan-Meier methodology will be used to estimate the 2-year overall survival.
measure: Progression-free survival
time frame: From transplantation to disease relapse or death, assessed up to 2 years post-transplant
description: Kaplan-Meier methodology will be used to estimate the 2-year progression-free survival.
measure: Rates of minimal residual disease (MRD)
time frame: At days 28, and +80 to +90 post-transplant
description: MRD will be assessed using multi-color flow cytometry and next generation sequencing in conjunction with functional imaging (i.e., positron emission tomography-computed tomography). The proportion who achieve MRD will be estimated along with an exact 95% confidence interval.
arm group label: Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
arm group type: Experimental
description: Patients receive 211At-OKT10-B10 IV continuously on day -10 to day - 4 (approximately day -7) and melphalan via infusion on day -2. Patients then undergo HCT on day 0.
intervention type: Biological
intervention name: Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
description: Given IV
arm group label: Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
other name: 211At-OKT10-B10
other name: [211At]OKT10-B10
other name: Astatine 211-labeled Anti-CD38 Monoclonal Antibody OKT10-B10
other name: Astatine At 211 Anti-CD38 MoAb OKT10-B10
other name: Astatine-211-OKT10-B10
other name: At211-OKT10-B10
intervention type: Drug
intervention name: Melphalan
description: Given via infusion
arm group label: Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
other name: Alanine Nitrogen Mustard
other name: CB-3025
other name: L-PAM
other name: L-Phenylalanine Mustard
other name: L-Sarcolysin
other name: L-Sarcolysin Phenylalanine mustard
other name: L-Sarcolysine
other name: Melphalanum
other name: Phenylalanine Mustard
other name: Phenylalanine Nitrogen Mustard
other name: Sarcoclorin
other name: Sarkolysin
other name: WR-19813
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo PBSC transplantation
arm group label: Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
other name: PBPC transplantation
other name: PBSCT
other name: Peripheral Blood Progenitor Cell Transplantation
other name: Peripheral Stem Cell Support
other name: Peripheral Stem Cell Transplant
other name: Peripheral Stem Cell Transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Damian J. Green
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Damian J. Green
phone: 206-667-5398
email: dgreen@fredhutch.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Antineoplastic Agents, Immunological
mesh term: Melphalan
mesh term: Mechlorethamine
mesh term: Nitrogen Mustard Compounds
mesh term: Daratumumab
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
sharing ipd: No