<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/NCT02223312</url>
  </required_header>
  <id_info>
    <org_study_id>KiroVAX002.2</org_study_id>
    <secondary_id>BSK01 Dendritic cell vaccine</secondary_id>
    <nct_id>NCT02223312</nct_id>
  </id_info>
  <brief_title>Therapy for Progressive and/or Refractory Hematologic Malignancies</brief_title>
  <official_title>Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Low Dose GM-CSF, in Patients With Progressive and/or Refractory Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kiromic BioPharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kiromic BioPharma Inc.</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>
      The purpose of this study is to evaluate the safety and effectiveness of Tumor Associated&#xD;
      Peptide Antigen (TAPA) pulsed dendritic cell (DC) vaccines in the treatment of progressive&#xD;
      and/or refractory hematologic malignancies (HM). We hypothesize that treatment of patients&#xD;
      with relapsed and/or refractory HM, without available potentially curative treatment options,&#xD;
      and whose neoplastic cells express at least one (1) TAPA of a defined panel of TAPAs, using&#xD;
      low-dose cyclophosphamide (CYP) followed by an autologous, monocyte-derived, TAPA-pulsed DC&#xD;
      vaccine and low-dose granulocyte macrophage colony stimulating factor (GM-CSF), will result&#xD;
      in TAPA-specific T-cell responses without significant toxicities. We also hypothesize CD4+&#xD;
      T-cell and CD8+ T-cell responses generated against specific TAPAs may translate into clinical&#xD;
      antitumor activity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients diagnosed with progressive and/or refractory hematologic malignancies, who have&#xD;
      failed conventional therapy and have no potentially curative therapeutic options available,&#xD;
      will be candidates for this Phase I/II study. Following confirmation of disease progression&#xD;
      and/or refractoriness, eligible patients who agree to participate and sign a consent form&#xD;
      will have their neoplastic cells and/or blood analyzed for the expression of a specific panel&#xD;
      of Tumor Associated Peptide Antigens (TAPAs), including SP17, Ropporin, AKAP4, PTTG1 and&#xD;
      Span-xb. Patients whose tumors express one (1) or more of these TAPAs will receive three (3)&#xD;
      days of subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) to increase&#xD;
      bone marrow production of monocytes and dendritic cell (DC) precursors, and peripheral blood&#xD;
      mononuclear cells will be obtained by phlebotomy and/or leukapheresis for generation of&#xD;
      autologous DCs. Patient's DCs will be generated at Kiromic's Cell Processing GMP facility,&#xD;
      according to established Standard Operating Procedures, and activated by pulsing/loading them&#xD;
      with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of&#xD;
      low-dose cyclophosphamide prior to each vaccination with TAPA-pulsed DCs to decrease Treg&#xD;
      activity. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 x 107 DCs at least&#xD;
      two (2) days following cyclophosphamide administration. DC vaccination schedule will be once&#xD;
      every fourteen (14) days via subcutaneous (SC) and intradermal (ID) injections for a total of&#xD;
      6 vaccinations. Low dose GM-CSF will also be administered SC for five (5) consecutive days,&#xD;
      starting three (3) to six (6) hours after each TAPA-pulsed DC treatment, to optimize immune&#xD;
      response and DC viability in vivo. Patients will be followed on a weekly basis (or more&#xD;
      frequently if required) to evaluate treatment-related toxicity. Immune responses and&#xD;
      anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping&#xD;
      rules for the study will be defined based on toxicity/tolerability (Phase I) and/or immune&#xD;
      efficacy (Phase II).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Sponsor decision to discontinue study.&#xD;
  </why_stopped>
  <start_date type="Actual">July 28, 2017</start_date>
  <completion_date type="Anticipated">January 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events that occur due to toxicity of low-dose CYP followed by TAPA-pulsed DC therapy and low-dose GM-CSF administration</measure>
    <time_frame>Every 7 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunological efficacy as indicated by T-cell cytokine levels</measure>
    <time_frame>up to 5 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test</measure>
    <time_frame>up to 5 months</time_frame>
    <description>DTH skin test will be performed 8-10 days before vaccine administration. DTH response will be evaluated again at days 28 and 70 of the trial as well as 14 and 60 days after the trial has ended.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cancer</condition>
  <condition>Hematologic Malignancies</condition>
  <arm_group>
    <arm_group_label>TAPA-pulsed DC vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subject will take low-dose cyclophosphamide by mouth for 5 days starting 7 days prior to the vaccine cycle. The vaccine contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered SQ with low-dose GM-CSF following the low-dose cyclophosphamide cycle. A total of six (6) cycles of cyclophosphamide and six (6) DC vaccines cycles will be administered alternating every 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TAPA-pulsed DC vaccine</intervention_name>
    <description>A cycle of low-dose cyclophosphamide (100mg/day) by mouth for 5 days starting seven 7 days prior to the DC vaccine cycle to reduce Treg activity. Low-dose cyclophosphamide will be taken every 14 days for six 6 cycles. A total of 6 vaccines containing 1 x 10^7 TAPA-pulsed DC will be administered SQ every 14 days. The DC vaccine is given on Day 1 of the DCV cycle plus low-dose GM-CSF 50mcg/day SQ x 5 days (Day 1 to Day 4). GM-CSF is administered for 5 days to increase monocyte production and dendritic cell precursors to optimize immune responses.</description>
    <arm_group_label>TAPA-pulsed DC vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to provide informed consent.&#xD;
&#xD;
          2. Patients at least eighteen (18) years of age diagnosed with the following&#xD;
             histologically proven, progressive and/or refractory HM following standard therapy:&#xD;
             Multiple Myeloma (MM), Hodgkins Disease (HD), Non-Hodgkins Lymphoma (NHL) and Chronic&#xD;
             Lymphocytic Leukemia (CLL), and without potentially curative therapeutic options, will&#xD;
             be eligible.&#xD;
&#xD;
          3. Expression of one (1) or more of the following TAPAs: SP17, AKAP4, Ropporin, PTTG1 and&#xD;
             Span-xb, by either RT-PCR and/or immunocytochemistry, Western blotting or ELISA, in&#xD;
             neoplastic cells and/or blood.&#xD;
&#xD;
          4. Presence of measurable or evaluable disease.&#xD;
&#xD;
          5. Patients must not have any active infectious process.&#xD;
&#xD;
          6. Patients must have a negative test for HIV, Hepatitis A, B, and C.&#xD;
&#xD;
          7. Patients must not be receiving active immunosuppressive therapy.&#xD;
&#xD;
          8. Patients must have discontinued systemic antineoplastic therapy (including systemic&#xD;
             corticosteroids) at least four (4) weeks prior to enrollment.&#xD;
&#xD;
          9. Patients may not have any known allergy to GM-CSF.&#xD;
&#xD;
         10. Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood&#xD;
             obtained by phlebotomy and/or consent to leukapheresis for DC generation.&#xD;
&#xD;
         11. Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl,&#xD;
             AST and ALT ≤ 4X upper limit of normal range).&#xD;
&#xD;
         12. Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000/mm3,&#xD;
             neutrophils ≥ 750/mm3, hemoglobin ≥ 10 g/dl).&#xD;
&#xD;
         13. Karnofsky performance status ≥ 70%.&#xD;
&#xD;
         14. Expected survival ≥ 6 months.&#xD;
&#xD;
         15. Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A*01, and/or&#xD;
             HLA-A-*02, and/or HLA-A*24 restriction.&#xD;
&#xD;
         16. Either a female or male of reproductive capacity wishing to participate in this study&#xD;
             must be using, or agree to use, one or more types of birth control during the entire&#xD;
             study and for 3 months after completing the study. Birth control methods may include&#xD;
             condoms, diaphragms, birth control pills, spermicidal gels or foams, anti-gonadotropin&#xD;
             injections, intrauterine devices (IUD), surgical sterilization, or subcutaneous&#xD;
             implants. Another choice is for a subject's sexual partner to use one of these birth&#xD;
             control methods. Women of reproductive capacity will be required to undergo a urine&#xD;
             pregnancy test before completion of the post-screening informed consent process.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients without confirmed progressive and/or refractory MM, HD, NHL and CLL, or those&#xD;
             with confirmed progressive and/or refractory MM, HD, NHL and CLL but who have a&#xD;
             potentially curative therapeutic intervention available, are excluded from the study.&#xD;
&#xD;
          2. Patients without measurable or evaluable disease.&#xD;
&#xD;
          3. Patients receiving cytotoxic therapy, radiation therapy, immunotherapy or non-topical&#xD;
             steroids for HM within four (4) weeks of enrollment.&#xD;
&#xD;
          4. Active immunosuppressive or cytotoxic therapy (excluding topical steroids) for any&#xD;
             other condition.&#xD;
&#xD;
          5. Persistent fever (&gt;24 hours) documented by repeated measurement or active,&#xD;
             uncontrolled infection within 4 weeks of enrollment.&#xD;
&#xD;
          6. Active ischemic heart disease or history of myocardial infarction within six months.&#xD;
&#xD;
          7. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus&#xD;
             (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis&#xD;
             (RA).&#xD;
&#xD;
          8. Pregnancy or breast feeding.&#xD;
&#xD;
          9. Active second invasive malignancy, other than basal cell carcinoma of the skin.&#xD;
&#xD;
         10. Life expectancy of less than 6 months.&#xD;
&#xD;
         11. Patients with contraindications to CYP and/or GM-CSF.&#xD;
&#xD;
         12. Patients who have received organ transplantations.&#xD;
&#xD;
         13. Patients with psychological or geographic conditions that prevent adequate follow-up&#xD;
             or compliance with the study protocol.&#xD;
&#xD;
         14. Patients with documented primary or secondary central nervous system (CNS) involvement&#xD;
             at any time during disease course are excluded from the study.&#xD;
&#xD;
         15. Patient with HLA-A alleles not belonging to any of the following subtypes: HLA-A*01,&#xD;
             or HLA-A*02, or HLA-A*24.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>August 24, 2018</last_update_submitted>
  <last_update_submitted_qc>August 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</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>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_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/NCT02223312
org study id: KiroVAX002.2
secondary id: BSK01 Dendritic cell vaccine
nct id: NCT02223312
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and effectiveness of Tumor Associated
      Peptide Antigen (TAPA) pulsed dendritic cell (DC) vaccines in the treatment of progressive
      and/or refractory hematologic malignancies (HM). We hypothesize that treatment of patients
      with relapsed and/or refractory HM, without available potentially curative treatment options,
      and whose neoplastic cells express at least one (1) TAPA of a defined panel of TAPAs, using
      low-dose cyclophosphamide (CYP) followed by an autologous, monocyte-derived, TAPA-pulsed DC
      vaccine and low-dose granulocyte macrophage colony stimulating factor (GM-CSF), will result
      in TAPA-specific T-cell responses without significant toxicities. We also hypothesize CD4+
      T-cell and CD8+ T-cell responses generated against specific TAPAs may translate into clinical
      antitumor activity.
Patients diagnosed with progressive and/or refractory hematologic malignancies, who have
      failed conventional therapy and have no potentially curative therapeutic options available,
      will be candidates for this Phase I/II study. Following confirmation of disease progression
      and/or refractoriness, eligible patients who agree to participate and sign a consent form
      will have their neoplastic cells and/or blood analyzed for the expression of a specific panel
      of Tumor Associated Peptide Antigens (TAPAs), including SP17, Ropporin, AKAP4, PTTG1 and
      Span-xb. Patients whose tumors express one (1) or more of these TAPAs will receive three (3)
      days of subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) to increase
      bone marrow production of monocytes and dendritic cell (DC) precursors, and peripheral blood
      mononuclear cells will be obtained by phlebotomy and/or leukapheresis for generation of
      autologous DCs. Patient's DCs will be generated at Kiromic's Cell Processing GMP facility,
      according to established Standard Operating Procedures, and activated by pulsing/loading them
      with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of
      low-dose cyclophosphamide prior to each vaccination with TAPA-pulsed DCs to decrease Treg
      activity. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 x 107 DCs at least
      two (2) days following cyclophosphamide administration. DC vaccination schedule will be once
      every fourteen (14) days via subcutaneous (SC) and intradermal (ID) injections for a total of
      6 vaccinations. Low dose GM-CSF will also be administered SC for five (5) consecutive days,
      starting three (3) to six (6) hours after each TAPA-pulsed DC treatment, to optimize immune
      response and DC viability in vivo. Patients will be followed on a weekly basis (or more
      frequently if required) to evaluate treatment-related toxicity. Immune responses and
      anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping
      rules for the study will be defined based on toxicity/tolerability (Phase I) and/or immune
      efficacy (Phase II).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events that occur due to toxicity of low-dose CYP followed by TAPA-pulsed DC therapy and low-dose GM-CSF administration
time frame: Every 7 days
measure: Immunological efficacy as indicated by T-cell cytokine levels
time frame: up to 5 months
measure: Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test
time frame: up to 5 months
description: DTH skin test will be performed 8-10 days before vaccine administration. DTH response will be evaluated again at days 28 and 70 of the trial as well as 14 and 60 days after the trial has ended.
arm group label: TAPA-pulsed DC vaccine
arm group type: Experimental
description: The subject will take low-dose cyclophosphamide by mouth for 5 days starting 7 days prior to the vaccine cycle. The vaccine contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered SQ with low-dose GM-CSF following the low-dose cyclophosphamide cycle. A total of six (6) cycles of cyclophosphamide and six (6) DC vaccines cycles will be administered alternating every 14 days.
intervention type: Biological
intervention name: TAPA-pulsed DC vaccine
description: A cycle of low-dose cyclophosphamide (100mg/day) by mouth for 5 days starting seven 7 days prior to the DC vaccine cycle to reduce Treg activity. Low-dose cyclophosphamide will be taken every 14 days for six 6 cycles. A total of 6 vaccines containing 1 x 10^7 TAPA-pulsed DC will be administered SQ every 14 days. The DC vaccine is given on Day 1 of the DCV cycle plus low-dose GM-CSF 50mcg/day SQ x 5 days (Day 1 to Day 4). GM-CSF is administered for 5 days to increase monocyte production and dendritic cell precursors to optimize immune responses.
arm group label: TAPA-pulsed DC vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Hematologic Neoplasms