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NCT03735589 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: i 60417NCI-2018-02337P50CA159981
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events as assessed by Cancer Therapy Evaluation Program (CTEP) version 4 of the Common Terminology Criteria for Adverse Events (CTCAE)

  Up to 12 months

• Dose-limiting toxicities (DLT) assessed by CTCAE version 5

  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.

  Up to 14 days after intraperitoneal (IP) infusion of nCTLs

• Change in immune response

  Change in immune response will be measured by the increase in the number of CD3+CD8+NKG2D (high) natural killer cell-like cytotoxic T-lymphocyte (CTLs) (nCTLs) and the increase in total CD3+CD8+ CTLs recovered in the peritoneal washes with evaluation on day 0 versus day 2. The analysis will consist of an analysis-of-covariance (ANCOVA) for the outcome of post-pre ACT treatment cell count with a factor for dose and sampling time 48 hrs +/- 24 hrs.

  From baseline (day 0) to day 2 (48 hours after adoptive cell therapy [ACT]) administration

• Persistence of nCTLs after their adoptive transfer

  At day 0 will obtain peritoneal material (outflow and washes) directly before i.p. infusion of nCTLs, as well as day 2 (48 hours +/- 24 hours), day 7 (+/- 2 days), 2 weeks (14 days +/- 2 days) and 4 weeks (28 days +/- 3 days) later.

  Up to 4 weeks

Secondary Outcomes (1)

• T cell populations and higher anti-tumor responses

  Up to 4 weeks

Other Outcomes (2)

• Progression-free survival assessed by immune-related response criteria (irRECIST)

  Up to 12 months

• Overall survival assessed by irRECIST

  Up to 12 months

Study Arms (1)

Treatment (nCTLs, alpha-DC1 vaccine)

EXPERIMENTAL

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.

Biological: Alpha-type-1 Polarized Dendritic Cells; Biological: Autologous Natural Killer Cell-like CTLs

Interventions

Alpha-type-1 Polarized Dendritic Cells BIOLOGICAL

Given ID

Also known as: alphaDC1

Treatment (nCTLs, alpha-DC1 vaccine)

Autologous Natural Killer Cell-like CTLs BIOLOGICAL

Given IP

Also known as: 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

Treatment (nCTLs, alpha-DC1 vaccine)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Emese Zsiros, MD, PhD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 8, 2018
• Study Start: December 15, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

US (1)