Clinical Trials /

Consolidation Therapy in Patients With Hematologic Malignancies

NCT02709993

Description:

The purpose of this study is to determine the safety and efficacy of Tumor Associated Peptide Antigen (TAPA) pulsed dendritic cell (DC) vaccines in the treatment of hematologic malignancies.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Consolidation Therapy in Patients With Hematologic Malignancies
  • Official Title: Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Low Dose GM-CSF, As Consolidation Treatment in Patients With Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: KiroVAX001
  • SECONDARY ID: BSK01 Dendritic cell vaccine
  • NCT ID: NCT02709993

Conditions

  • Cancer
  • Hematologic Malignancies

Interventions

DrugSynonymsArms
TAPA-pulsed DC vaccineTAPA-pulsed DC vaccine

Purpose

The purpose of this study is to determine the safety and efficacy of Tumor Associated Peptide Antigen (TAPA) pulsed dendritic cell (DC) vaccines in the treatment of hematologic malignancies.

Detailed Description

      Patients diagnosed with hematologic malignancies (as defined) who have responded to
      conventional therapy, and without any potentially curative therapeutic intervention, will be
      candidates for this Phase I/II study. Following confirmation of disease response to
      conventional antineoplastic therapy, eligible patients who agree to participate and sign a
      consent form will have their tumor 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
      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 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 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 or cytologically
                 proven Multiple Myeloma (MM), Hodgkins Disease (HD), Non-Hodgkins Lymphoma (NHL),
                 Chronic Myelogenous Leukemia (CML), Acute Lymphocytic Leukemia (ALL), Acute
                 Myelogenous Leukemia (AML) and Chronic Lymphocytic Leukemia (CLL), who have responded
                 to standard, first-line antineoplastic therapy, as defined using standard response
                 criteria for the specific hematologic malignancy (HM), and have no additional
                 potentially curative therapeutic intervention available, will be eligible to
                 participate in this study.
    
              3. Expression of one (1) or more of the following TAPAs: SP17, AKAP4, Ropporin, PTTG1 and
                 Span-xb, by either reverse transcriptase polymerase chain reaction (RT-PCR) and/or
                 immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood.
    
              4. Presence of measurable or evaluable disease (unless patient has achieved a complete
                 response (CR) following first-line antineoplastic therapy).
    
              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 systemic
                 corticosteroids and excluding tyrosine kinase inhibitors for CML) at least four (4)
                 weeks prior to enrollment.
    
              9. Patients may not have any known allergy to CYP and/or 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,
                 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 g/dl).
    
             13. Karnofsky performance status ≥ 70%.
    
             14. Expected survival ≥ 6 months.
    
             15. Patient Human Leukocyte Antigen (HLA) typing should demonstrate HLA-A*01, and/or
                 HLA-A*02, and/or HLA-A*24 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 with HM, as previously defined, without confirmed response to standard,
                 first-line antineoplastic therapy, and/or who do not fulfill all Inclusion Criteria as
                 stated, will be ineligible to participate in this study.
    
              2. Patients with HM who have undergone myeloablative systemic therapy are ineligible to
                 participate in this study.
    
              3. Patients without measurable or evaluable disease (unless patients achieved a complete
                 response (CR) following 1st-line antineoplastic therapy).
    
              4. Patients receiving cytotoxic therapy, radiation therapy, immunotherapy or non-topical
                 steroids for HM within four (4) weeks of enrollment, excluding tyrosine kinase
                 inhibitors in patients with CML.
    
              5. Active immunosuppressive or cytotoxic therapy (excluding topical steroids) for any
                 other condition.
    
              6. Persistent fever (>24 hours) documented by repeated measurement or active,
                 uncontrolled infection within 4 weeks of enrollment.
    
              7. Active ischemic heart disease or history of myocardial infarction within six months.
    
              8. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus
                 (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis
                 (RA).
    
              9. Pregnancy or breast feeding.
    
             10. Patients with an active second invasive malignancy, other than basal cell carcinoma of
                 the skin.
    
             11. Life expectancy of less than 6 months.
    
             12. Patients with contraindications to CYP and/or GM-CSF.
    
             13. Patients who have received organ transplantations.
    
             14. Patients with psychological or geographic conditions that prevent adequate follow-up
                 or compliance with the study protocol.
    
             15. Patients diagnosed with primary central nervous system (CNS) or with CNS
                 metastases/involvement, at any time during the disease course, are excluded from the
                 study.
    
             16. Patients with HLA-A alleles not belonging to any of the following subtypes: HLA-A*01,
                 or HLA-A*02, or HLA-A*24.
          
    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, Inc.

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