Clinical Trials /

Specialized Immune Cells (nCTLs) and a Vaccine (Alpha-type-1 Polarized Dendritic Cells) in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT03735589

Description:

This phase I/IIa trial studies the side effects and best dose of a type of specialized immune cell (natural killer cell-like cytotoxic T-lymphocytes (CTLs) (nCTLs) and how well they work when given with a vaccine (alpha-type-1 polarized dendritic cells) in treating patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. nCTLs are immune cells that are isolated from each patient?s blood and "taught" in the laboratory how to recognize and eliminate tumor cells. These "educated" immune cells are then given back to the patient. An alpha-type-1 polarized dendritic cell vaccine is another population of "educated" immune cells that work to support the infused nCTLs. Giving nCTLS with a dendritic cell vaccine may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Specialized Immune Cells (nCTLs) and a Vaccine (Alpha-type-1 Polarized Dendritic Cells) in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: A Phase I/IIa Safety and Immunologic Efficacy Trial of Intraperitoneal Induction of CTLs Combined With Alpha-Dendritic Cell Vaccine for Primary Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: i 60417
  • SECONDARY ID: NCI-2018-02337
  • SECONDARY ID: i 60417
  • SECONDARY ID: P30CA016056
  • SECONDARY ID: P50CA159981
  • NCT ID: NCT03735589

Conditions

  • Stage II Fallopian Tube Cancer AJCC v8
  • Stage II Ovarian Cancer AJCC v8
  • Stage II Primary Peritoneal Cancer AJCC v8
  • Stage IIA Fallopian Tube Cancer AJCC v8
  • Stage IIA Ovarian Cancer AJCC v8
  • Stage IIA Primary Peritoneal Cancer AJCC v8
  • Stage IIB Fallopian Tube Cancer AJCC v8
  • Stage IIB Ovarian Cancer AJCC v8
  • Stage IIB Primary Peritoneal Cancer AJCC v8
  • Stage III Fallopian Tube Cancer AJCC v8
  • Stage III Ovarian Cancer AJCC v8
  • Stage III Primary Peritoneal Cancer AJCC v8
  • Stage IIIA Fallopian Tube Cancer AJCC v8
  • Stage IIIA Ovarian Cancer AJCC v8
  • Stage IIIA Primary Peritoneal Cancer AJCC v8
  • Stage IIIA1 Fallopian Tube Cancer AJCC v8
  • Stage IIIA1 Ovarian Cancer AJCC v8
  • Stage IIIA2 Fallopian Tube Cancer AJCC v8
  • Stage IIIA2 Ovarian Cancer AJCC v8
  • Stage IIIB Fallopian Tube Cancer AJCC v8
  • Stage IIIB Ovarian Cancer AJCC v8
  • Stage IIIB Primary Peritoneal Cancer AJCC v8
  • Stage IIIC Fallopian Tube Cancer AJCC v8
  • Stage IIIC Ovarian Cancer AJCC v8
  • Stage IIIC Primary Peritoneal Cancer AJCC v8
  • Stage IV Fallopian Tube Cancer AJCC v8
  • Stage IV Ovarian Cancer AJCC v8
  • Stage IV Primary Peritoneal Cancer AJCC v8
  • Stage IVA Fallopian Tube Cancer AJCC v8
  • Stage IVA Ovarian Cancer AJCC v8
  • Stage IVA Primary Peritoneal Cancer AJCC v8
  • Stage IVB Fallopian Tube Cancer AJCC v8
  • Stage IVB Ovarian Cancer AJCC v8
  • Stage IVB Primary Peritoneal Cancer AJCC v8

Interventions

DrugSynonymsArms
Alpha-type-1 Polarized Dendritic CellsalphaDC1Treatment (nCTLs, alpha-DC1 vaccine)
Autologous Natural Killer Cell-like CTLsAutologous aDC1-induced CTLs, Autologous CTLs Sensitized Ex-vivo with Autologous TAA-loaded alphaDC1, Autologous Natural Killer-like Cytotoxic Lymphocytes, Autologous nCTLs, Autologous NK-like CTLs, In Vitro DC-sensitized CTLs, n-vitro DC-sensitized Autologous CTLs, Therapeutic nCTLs, Tumor Neo-antigen-specific nCTLsTreatment (nCTLs, alpha-DC1 vaccine)

Purpose

This phase I/IIa trial studies the side effects and best dose of a type of specialized immune cell (natural killer cell-like cytotoxic T-lymphocytes (CTLs) (nCTLs) and how well they work when given with a vaccine (alpha-type-1 polarized dendritic cells) in treating patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. nCTLs are immune cells that are isolated from each patient?s blood and "taught" in the laboratory how to recognize and eliminate tumor cells. These "educated" immune cells are then given back to the patient. An alpha-type-1 polarized dendritic cell vaccine is another population of "educated" immune cells that work to support the infused nCTLs. Giving nCTLS with a dendritic cell vaccine may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Detailed Description

      PRIMARY OBJECTIVES I. To evaluate the safety, tolerability, and feasibility of
      intraperitoneal (i.p.) administration of autologous tumor loaded DC vaccines (alpha-type-1
      polarized dendritic cell [alphaDC1]) combined with intradermally administered aDC1 .(Safety
      [Phase I aspect]) II. To measure the intraperitoneal induction and persistence of aDCI
      induced sensitized cytotoxic T Cells (CTLs), which express natural killer (NK) cell-like
      features (nCTLs) and total CTLs following intraperitoneal administration of aDC1. (Local
      Immunologic Efficacy [Phase II aspect])

      SECONDARY OBJECTIVES I. To study the T cell populations generated that correlates with higher
      anti-tumor responses.

      EXPLORATORY OBJECTIVES I. To evaluate the progression-free survival and overall survival of
      patients treated with this regimen.

      OUTLINE: This is a phase I, dose-escalation study of nCTLs, followed by a phase IIa study.

      Patients receive the alpha-type-1 polarized dendritic cell vaccine intradermally (ID) 2 weeks
      before day 0, on day 0, and on day 28. Patients also receive nCTLs intraperitoneally (IP)
      over 15-30 minutes on day 0. In the absence of unacceptable side effects, patients may
      receive the alpha-type-1 polarized dendritic cell vaccine every 1-3 months at the discretion
      of the physician.

      After completion of study treatment, patients are followed up at 14 days, then at 6 and 12
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nCTLs, alpha-DC1 vaccine)ExperimentalPatients receive the alpha-type-1 polarized dendritic cell vaccine ID 2 weeks before day 0, on day 0, and on day 28. Patients also receive aDC1 IP over 3-10 seconds on day 0. In the absence of unacceptable side effects, patients may receive the alpha-type-1 polarized dendritic cell vaccine every 1-3 months at the discretion of the physician.
  • Alpha-type-1 Polarized Dendritic Cells
  • Autologous Natural Killer Cell-like CTLs

Eligibility Criteria

        Inclusion Criteria:

          -  Eligible patients will be women with stages II-IV epithelial ovarian, fallopian tube,
             or primary peritoneal carcinoma with no radiologic evidence of disease (NED) or
             minimal disease burden after 1st line therapy. These patients would normally enter a
             period of observation after standard management.

          -  Life expectancy > 6 months.

          -  Have been informed of other treatment options.

          -  Patients must be reasonable candidates for intraperitoneal (IP) port placement with no
             prior evidence of persistent abdominal wall or intraperitoneal infections, renal
             toxicity, or bowel obstruction or fistula.

          -  Patients must have documented available tumor: at least 1 cm of bulk tumor mass
             collected at the time of primary or interval debulking surgery. The specimen may be
             obtained on this protocol or as part of other Institutional Review Board (IRB)
             approved tumor banking protocols.

          -  Patients should be free of active infection requiring antibiotics (with the exception
             of uncomplicated urinary tract infection [UTI]).

          -  Must have adequate venous access for apheresis. (Pheresis catheter placement for cell
             collection is allowed).

          -  Patient must agree to leukapheresis.

          -  Patients must agree to appropriate clinical monitoring to receive the study regimens.

          -  Absolute neutrophil count (ANC) greater than or equal to 1,000/uL.

          -  Platelets greater than or equal to 75,000/uL.

          -  Hemoglobin greater than or equal to 8.0 g/dL.

          -  Creatinine less than or equal to 2 x institutional upper limit normal (ULN).

          -  Bilirubin less than or equal to 1.5 x ULN.

          -  Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN.

          -  Alkaline phosphatase less than or equal to 3 x ULN.

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure.

          -  Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
             history: >= 50 years old and no menses for >= 1 year without an alternative medical
             cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
             of bilateral oophorectomy) or must have a negative urine or serum pregnancy test
             within 28 days of study treatment, confirmed prior to treatment.

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of
             0 or 1.

        Exclusion Criteria:

          -  Metastatic disease to the central nervous system and any site above diaphragm.

          -  Other serious illnesses (e.g., serious infections requiring antibiotics [with the
             exception of uncomplicated UTI], bleeding disorders).

          -  Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing
             of study agent. Concomitant hormonal therapies are allowed.

          -  Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic
             lupus erythematosus [SLE], ulcerative colitis, Crohn's Disease, multiple sclerosis
             [MS], ankylosing spondylitis) requiring chronic use of steroids or other
             immunosuppressives.

          -  Patients being chronically treated with immunosuppressive drugs such as cyclosporin,
             adrenocorticotropic hormone (ACTH), or systemic chronic corticosteroids. NOTE: Recent
             or current use of inhaled steroids is not exclusionary.

          -  Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g.,
             interleukin 2, interferon alpha or gamma, granulocyte colony stimulating factors,
             etc.) within 30 days prior to study entry.

               -  NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects
                  are prescribed a brief course of oral steroids, the use should be limited to less
                  than 7 days. Use of steroids before apheresis and immune assessment blood draws
                  will affect white blood cell function (wash out period of 1 week).

          -  Patients with a known immunodeficiency disease including cellular immunodeficiencies,
             hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary,
             or congenital immunodeficiencies. Specific testing is not required, however may be
             done as clinically indicated.

          -  Patients with uncontrolled diseases other than cancer may be excluded if after
             consultation with PI and research team it is decided it might affect the treatment
             efficacy or toxicity..

          -  Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with
             no peritoneal disease at initial diagnosis.

          -  Patients with a history of other invasive malignancies, with the exception of
             nonmelanoma skin cancer, are excluded if there is any evidence of other malignancy
             being present within the last three years. Patients are also excluded if their
             previous cancer treatment contraindicates this protocol therapy.

          -  Evidence of current drug or alcohol abuse or psychiatric impairment, which in the
             investigator's opinion will prevent completion of the protocol therapy or follow-up.
             Specific testing is not required, however may be done as clinically indicated.

          -  Any condition that in the opinion of principal investigator (PI) would preclude
             patient from successfully completing the protocol therapy or follow-up.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events as assessed by Cancer Therapy Evaluation Program (CTEP) version 4 of the Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame:Up to 12 months
Safety Issue:
Description:Will be used in the estimation of the maximum tolerated dose (MTD) and the accompanying of the dose escalation decisions. However, no formal analyses of DLTs are planned.

Secondary Outcome Measures

Measure:T cell populations and higher anti-tumor responses
Time Frame:Up to 4 weeks
Safety Issue:
Description:Will estimate the half-life of CD3/CD8/NKG2D (triple-positive nCTLs) cell counts and longitudinal changes CD3/CD8 cell counts (double-positive CTLs, which include both nCTLs and additional CTLs newly recruited CTLs from the circulation) cell counts as a function of dose and time. A nonlinear regression model with a random effect for subject (population pharmacokinetics [PK]) will be fit to a one-compartment kinetics first-order absorption model per dose level.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

February 21, 2020