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

NCT ID: NCT03735589

Last Updated: 2023-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-15

Study Completion Date

2025-12-01

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (nCTLs, alpha-DC1 vaccine)

Patients 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.

Group Type EXPERIMENTAL

Alpha-type-1 Polarized Dendritic Cells

Intervention Type BIOLOGICAL

Given ID

Autologous Natural Killer Cell-like CTLs

Intervention Type BIOLOGICAL

Given IP

Interventions

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Alpha-type-1 Polarized Dendritic Cells

Given ID

Intervention Type BIOLOGICAL

Autologous Natural Killer Cell-like CTLs

Given IP

Intervention Type BIOLOGICAL

Other Intervention Names

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alphaDC1 Autologous 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 nCTLs

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emese Zsiros, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2018-02337

Identifier Type: REGISTRY

Identifier Source: secondary_id

i 60417

Identifier Type: OTHER

Identifier Source: secondary_id

P50CA159981

Identifier Type: NIH

Identifier Source: secondary_id

View Link

i 60417

Identifier Type: -

Identifier Source: org_study_id