Brief Title
Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Official Title
A Phase I Open Label Clinical Trial Evaluating the Safety and Efficacy of Adoptive Transfer of NY-ESO-1 TCR Engineered Autologous T Cells in Combination With Decitabine in Patients With Recurrent or Treatment Refractory Ovarian Cancer
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.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of the autologous NY-ESO-1 redirected T cell
therapy in combination with decitabine and low-dose IL-2 in patients with treatment
refractory or recurrent epithelial or non-epithelial ovarian, primary peritoneal or fallopian
tube carcinoma.
SECONDARY OBJECTIVES:
I. To evaluate the persistence of genetically modified cells in the peripheral blood, and at
tumor sites.
II. To examine the effect of the treatment on tumor as measured by objective tumor response
and progression free survival, both assessed by immune-related Response Evaluation Criteria
in Solid Tumors (irRECIST).
III. To assess the occurrence of target antigen and/or major histocompatibality complex (MHC)
loss variants upon disease recurrence.
TERTIARY OBJECTIVES:
I. To evaluate the post treatment phenotype and functionality of genetically modified T cells
isolated from peripheral blood and from tumor sites.
II. To assess changes in immunoscore, Tregs, Myeloid cell subsets, and antigen spreading in
peripheral blood and tumor site.
III. To assess the influence of demographic and disease molecular characteristics on
treatment outcomes of complete response (CR) and overall survival (OS).
OUTLINE:
COURSE 1: Patients receive decitabine IV daily over 1 hour on days -8 to Day -6,
cyclophosphamide IV over 2 hours on days -4 and -3, and genetically engineered
NY-ESO-1-specific T lymphocytes IV and intraperitoneally (IP) on day 0. Followed by low-dose
IL-2 for 2 weeks from Day 1 to Day 14..
After completion of study treatment, patients are followed up monthly at 3-9 months, every 6
months for 4 years, and then annually for up to 15 years.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4
Secondary Outcome
Appearance of target antigen/major histocompatibility complex loss variants upon disease recurrence
Condition
Recurrent Fallopian Tube Carcinoma
Intervention
Aldesleukin
Study Arms / Comparison Groups
Treatment (decitabine, genetically modified T cells)
Description: 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..
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
9
Start Date
December 8, 2017
Completion Date
December 8, 2021
Primary Completion Date
December 8, 2020
Eligibility Criteria
Inclusion Criteria:
- 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
- Patient 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
Exclusion Criteria:
- 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
- NOTE: recent or current use of inhaled steroids is not exclusionary; if subjects
are prescribed a brief course of oral corticosteroids, the use should be limited
to less than 7 days
- 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])
- Patients with pulmonary function test abnormalities as evidenced by a forced
expiratory volume in 1 second to forced vital capacity ratio measurement (FEV1/FVC) <
70% of predicted for normality will be excluded
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Kunle Odunsi, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03017131
Organization ID
i 283616
Secondary IDs
NCI-2016-01477
Responsible Party
Sponsor
Study Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Kunle Odunsi, Principal Investigator, Roswell Park Cancer Institute
Verification Date
June 2020