Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT03017131 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: i 283616NCI-2016-01477P30CA016056P50CA159981
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of genetically modified T cells and decitabine in treating patients with recurrent or refractory epithelial or non-epithelial ovarian, primary peritoneal, or fallopian tube cancer that has come back or has not responded to previous treatments. White blood cells called T cells are collected via a process called leukapheresis, genetically modified to recognize and attack tumor cells, then given back to the patient. Decitabine may induce and increase the amount of the target protein NY-ESO-1 available on the surface of tumor cells. Giving genetically modified T cells and decitabine may kill more tumor cells.

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4

  The frequency of toxicities will be tabulated by grade across all dose levels and cycles.

  Up to 28 days post infusion

Secondary Outcomes (6)

• Appearance of target antigen/major histocompatibility complex loss variants upon disease recurrence

  Up to 15 years

• Clinical response rates

  Up to 15 years

• Duration of response

  Up to 15 years

• Immunological parameters associated with T cell persistence, bioactivity and functionality

  Up to 15 years

• Overall survival

  Up to 15 years

Study Arms (1)

Treatment (decitabine, genetically modified T cells)

EXPERIMENTAL

COURSE 1: Patients receive decitabine IV daily over 1 hour on days -8 to -6, cyclophosphamide IV over 2 hours on days -4 and -3, and genetically engineered NY-ESO-1-specific T lymphocytes IV and IP on day 0. Patients also receive aldesleukin SC BID on days 1-14..

Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Decitabine; Biological: Genetically Engineered NY-ESO-1-specific T Lymphocytes; Other: Laboratory Biomarker Analysis

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (decitabine, genetically modified T cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (decitabine, genetically modified T cells)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, genetically modified T cells)

Genetically Engineered NY-ESO-1-specific T Lymphocytes BIOLOGICAL

Given IV and IP

Treatment (decitabine, genetically modified T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (decitabine, genetically modified T cells)

Eligibility Criteria

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

You may qualify if:

• Patients with recurrent or refractory epithelial or non-epithelial ovarian, primary peritoneal or fallopian tube carcinoma who have received platinum containing chemotherapy and either has platinum refractory or resistant disease, or if plantinum sensitive disease, have received \>= 2 lines of chemotherapy. Subjects may have received PARP inhibitators , bevacizumab or immunotherapy. Non-epithelial tumors of the ovary include sarcomas, granulosa cell tumors and malignant germ cell tumors including chiriocarcinoma
• Have been informed of other treatment options
• Must be HLA- A\*02;01 positive; retesting is not required for patients who have previous documented HLA-A\*02;01 positivity
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \> 4 months
• At least 4 weeks from prior chemotherapy, radiotherapy or immunotherapy, or prior investigational agents
• Must have measurable disease as defined by irRECIST
• Must have adequate venous access for apheresis; (pheresis catheter placement for cell collection is allowed)
• Women of childbearing potential in agreement to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood; this may be a period of several years; methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used
• Leukocytes \>= 3 x 10\^9/L
• Absolute neutrophil count \>= 1 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin within normal institutional limits
• Aspartate Aminotransferases (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine level = 2X\< upper limit of normal (ULN): if creatinine \> 2XULN, creatinine clearance must be \> 60ml/min

You may not qualify if:

• Patients receiving any other investigational agents
• Patients with active brain metastases should be excluded from this clinical trial; patients with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible. Brain MRI as clinically indicated only
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, decitabine or other agents used in the study
• Prior malignancy (except non melanoma skin cancer) within 3 years
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• 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
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) as defined below, due to the immunosuppressive effects of cyclophosphamide used and the unknown risks associated with viral replication
• Positive serology for HIV
• Active hepatitis B infection as determined by a positive test for hepatitis B surface antigen (Ag)
• Active hepatitis C; patients will be screened for HCV antibody; if the HCV antibody is positive, a screening HCV ribonucleic acid (RNA) by any real time polymerase chain reaction (RT PCR) or branched deoxyribose nucleic acid (bDNA) assay must be performed at screening by a local laboratory with a Clinical Laboratory Improvement Act (CLIA) certification or its equivalent; eligibility will be determined based on a negative screening value; the test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided
• Serology (CMV immunoglobulin G \[IgG\]) positive for active CMV
• Received any previous gene therapy using an integrating vector within 6 months
• Pregnancy or breast-feeding
• Lack of availability of a patient for immunological and clinical follow up assessment
• Evidence or history of significant cardiac disease (including evidence or history of significant cardiac disease (including myocardial infarction \[MI\] in the past 6 months, significant cardiac arrhythmia, stage III or IV congestive heart failure \[CHF\]); cardiac stress test will be done as clinically indicated; (the specific test to be chosen at the discretion of the principal investigator \[PI\])

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

Interventions

aldesleukin; Cyclophosphamide; Decitabine; Injections

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Emese Zsiros, MD

  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: October 19, 2016
• First Posted: January 11, 2017
• Study Start: December 8, 2017
• Primary Completion: March 23, 2020
• Study Completion (Estimated): March 23, 2032
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

US (1)