Clinical Trials /

Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies

NCT02224599

Description:

Patients diagnosed with progressive and/or refractory solid malignancies, who have failed conventional therapy, and have no available, potentially curative therapeutic options, 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 an informed consent form will have their tumor cells/tissues 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treatment of Patients With Progressive and/or Refractory Solid Malignancies
  • Official Title: Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Low Dose Granulocyte-Macrophage Colony Stimulating Factor, in Patients With Progressive and/or Refractory Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: Kirovax 003
  • SECONDARY ID: BSK01 Dendritic cell vaccine
  • NCT ID: NCT02224599

Conditions

  • Progressive Solid Malignancies
  • Refractory Solid Malignancies
  • Cancer

Interventions

DrugSynonymsArms
TAPA-pulsed DC vaccineTAPA-pulsed DC vaccine

Purpose

Patients diagnosed with progressive and/or refractory solid malignancies (SM), who have failed conventional therapy, and have no available, potentially curative therapeutic options, 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 tumor cells/tissues 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.

Detailed Description

      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 performed for generation of autologous DCs.
      Patient's DCs will be generated in 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
      responses. Patients will be followed on a weekly basis (or more frequently if required) to
      evaluate treatment-related toxicity. Immune efficacy 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 immune efficacy (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, progressive
                 and/or refractory SM without available, potentially curative therapeutic options will
                 be eligible for participation.
    
              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 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.
    
              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 mL, and up to 500 mL, 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,
                 AST and 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. 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.
    
             16. Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A1 restriction.
    
            Exclusion Criteria:
    
              1. Patients without confirmed progressive and/or refractory SM using standard RECIST
                 criteria, or those with confirmed progressive and/or refractory SM using standard
                 RECIST criteria, but who may have available, potentially curative therapeutic options
                 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) to four (4)
                 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 of less than 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 participation in this study.
    
             16. Patients 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:First evaluation will be 8-10 days before first DC vaccine. Additional evaluations on days 14, 28, 42, 56, and 70 of trial as well as 14 and 60 days after the last vaccine administered.
    Measure:Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test
    Time Frame:up to 5 months
    Safety Issue:
    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

    Details

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

    Last Updated

    August 9, 2017