Clinical Trials /

Consolidation Therapy in Patients With Metastatic Solid Malignancies

NCT02705703

Description:

This study evaluates the effectiveness of Tumor Associated Peptide Antigens (TAPA) pulsed dendritic cell injections as a potential consolidation therapy for patients with metastatic solid malignancies (SM). The investigators hypothesize that treatment of patients with metastatic SM who demonstrate a tumor response, or whose disease remains stable, after conventional first-line systemic therapy AND who lack an available, potentially curative therapeutic intervention and whose tumor cells and/or blood express at least one (1) TAPA of a defined panel of TAPAs will result in TAPA-specific T-cell responses without significant toxicities. The investigators also hypothesize CD4+ and CD8+ T-cell responses generated against specific TAPAs may translate into clinical antitumor activity.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Consolidation Therapy in Patients With Metastatic Solid Malignancies
  • Official Title: Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen (TAPA)-Pulsed Dendritic Cell (DC) Therapy and Low Dose GM-CSF, as Consolidation Therapy in Patients With Metastatic Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: KiroVAX004
  • SECONDARY ID: BSK01 Dendritic cell vaccine
  • NCT ID: NCT02705703

Conditions

  • Cancer
  • Metastatic Solid Malignancies

Interventions

DrugSynonymsArms
TAPA-pulsed DC vaccineTAPA-pulsed DC vaccine

Purpose

This study evaluates the effectiveness of Tumor Associated Peptide Antigens (TAPA) pulsed dendritic cell injections as a potential consolidation therapy for patients with metastatic solid malignancies (SM). The investigators hypothesize that treatment of patients with metastatic SM who demonstrate a tumor response, or whose disease remains stable, after conventional first-line systemic therapy AND who lack an available, potentially curative therapeutic intervention and whose tumor cells and/or blood express at least one (1) TAPA of a defined panel of TAPAs will result in TAPA-specific T-cell responses without significant toxicities. The investigators also hypothesize CD4+ and CD8+ T-cell responses generated against specific TAPAs may translate into clinical antitumor activity.

Detailed Description

      Patients diagnosed with metastatic solid malignancies (SM), who have responded or whose
      disease remains stable following first line systemic therapy, and without available,
      potential curative therapeutic options, will be candidates for this Phase I/II study.
      Potentially 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, AKAP-4, PTTG1, Span-xb,
      Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1. 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 whole blood will be obtained by phlebotomy and/or leukapheresis for
      generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing
      Good Manufacturing Process (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 responses. 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 responses (Phase II).
    

Trial Arms

NameTypeDescriptionInterventions
TAPA-pulsed DC vaccineExperimentalThe 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.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Ability to provide informed consent.
    
              2. Patients at least eighteen (18) years of age with histologically proven metastatic
                 solid malignancies (SM) AND whose SM demonstrates a response, or whose disease remains
                 stable, after conventional, first-line systemic therapy, AND who lack any available,
                 potentially curative therapeutic intervention, will be eligible for participation in
                 this study.
    
              3. Expression of one (1) or more of the following TAPAs; Sp17, AKAP-4, Ropporin, PTTG-1,
                 Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1, by either reverse transcriptase
                 polymerase chain reaction (RT-PCR) and/or immunocytochemistry, Western blotting or
                 ELISA, in neoplastic cells and/or blood. For HER-2/neu expression, positive FISH
                 results are acceptable. All lab tests will be performed in a CLIA certified facility
    
              4. Presence of measurable or evaluable disease.
    
              5. Patients must not have any active infectious process.
    
              6. Patients must have a negative test for HIV, Hepatitis A, B, and C.
    
              7. Patients must not be receiving active immunosuppressive therapy.
    
              8. Patients must have discontinued systemic antineoplastic therapy (including endocrine
                 and biological agents, as well as systemic corticosteroids) at least three (3) to four
                 (4) weeks prior to enrollment. Toxicities from previous therapies must be grade 1 or
                 less.
    
              9. Patients may not have any known allergy to GM-CSF.
    
             10. Patients must be willing to provide at least 250 mls of whole blood obtained by
                 phlebotomy and/or consent to leukapheresis for DC generation.
    
             11. Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl,
                 aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 4X upper limit of normal
                 range).
    
             12. Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3,
                 neutrophils ≥ 750/mm3, hemoglobin ≥ 10.0 g/dl).
    
             13. Karnofsky performance status ≥ 70%.
    
             14. Expected survival ≥ 6 months.
    
             15. Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A1 restriction.
    
             16. Either a female or male of reproductive capacity wishing to participate in this study
                 must be using, or agree to use, one or more types of birth control during the entire
                 study and for 3 months after completing the study. Birth control methods may include
                 condoms, diaphragms, birth control pills, spermicidal gels or foams, anti-gonadotropin
                 injections, intrauterine devices (IUD), surgical sterilization, or subcutaneous
                 implants. Another choice is for a subject's sexual partner to use one of these birth
                 control methods. Women of reproductive capacity will be required to undergo a urine
                 pregnancy test before completion of the post-screening informed consent process.
    
            Exclusion Criteria:
    
              1. Patients without confirmed metastatic SM and/or response to conventional, first-line
                 systemic therapy using standard RECIST criteria, or patients with confirmed metastatic
                 SM and/or response to conventional, first-line systemic therapy using standard RECIST
                 criteria, but who have an available, potentially curative therapeutic option will be
                 excluded from participation in this study.
    
              2. Patients without measurable or evaluable disease.
    
              3. Patients receiving cytotoxic therapy (including endocrine and biological agents),
                 radiation therapy, immunotherapy or non-topical steroids, within three (3) weeks of
                 enrollment.
    
              4. Active immunosuppressive therapy (excluding topical steroids) for any other condition.
    
              5. Persistent fever (>24 hours) documented by repeated measurement or active,
                 uncontrolled infection within 4 weeks of enrollment.
    
              6. Active ischemic heart disease or history of myocardial infarction within six months.
    
              7. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus
                 (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis
                 (RA).
    
              8. Pregnancy or breast feeding.
    
              9. Active second invasive malignancy, other than basal cell carcinoma of the skin.
    
             10. Life expectancy ≤ 6 months.
    
             11. Patients with contraindications to CYP and/or GM-CSF.
    
             12. History of allergy to CYP and/or GM-CSF.
    
             13. Patients who have received organ transplants.
    
             14. Patients with psychological or geographic conditions that prevent adequate follow-up
                 or compliance with the study protocol.
    
             15. Patients diagnosed with central nervous system (CNS) metastases or involvement at any
                 time during disease course are excluded from the study.
    
             16. Patient without HLA-A1 restriction.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of adverse events due to administration of TAPA-pulse DC vaccine
    Time Frame:every 7 days up to 5 months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Immunological efficacy as indicated by T-cell cytokine levels
    Time Frame:up to 5 months
    Safety Issue:
    Description:
    Measure:Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test
    Time Frame:up to 5 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Kiromic, LLC

    Last Updated

    August 10, 2017