Genetically Modified T Cells + Decitabine for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: Corticosteroids, Hydroxyurea, Immunomodulators

Disqualifiers: Brain metastases, Prior malignancy, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of using genetically modified T cells and decitabine to treat certain types of ovarian cancer that have recurred or resisted other treatments. Researchers collect and modify T cells, a type of white blood cell, to better recognize and attack cancer cells before returning them to the patient. Decitabine, a chemotherapy drug, increases a specific protein on cancer cells, making them more visible to the T cells. This study may suit patients with ovarian, primary peritoneal, or fallopian tube cancer who have previously undergone chemotherapy and are HLA-A*02:01 positive. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational agents or certain medications like chronic corticosteroids within 30 days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that decitabine, used to treat ovarian cancer, is generally safe but can have serious side effects. One study found that it often causes myelosuppression, meaning the bone marrow produces fewer blood cells. This can lead to infections due to low white blood cell counts. While decitabine can help fight cancer, it requires careful monitoring.

Genetically modified T cells have been mostly well-tolerated by past patients. A clinical trial found that these T cells, designed to attack cancer cells, remained active in the body for over 100 days in some cases. This suggests they can be effective for a while, but researchers continue to study all possible side effects.

Both treatments are being tested in early clinical trials, so researchers are still learning about their safety. These trials aim to better understand all possible side effects. Participants in these trials receive close monitoring to manage any risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy and surgery approaches for ovarian cancer, this treatment uses genetically engineered NY-ESO-1-specific T lymphocytes, which are designed to specifically recognize and attack cancer cells. Researchers are excited because this method involves reprogramming the patient's own immune cells to target the cancer more precisely, potentially leading to fewer side effects compared to traditional treatments. Additionally, the treatment pairs these modified T cells with decitabine, a drug that may enhance the immune response by altering the environment around the tumor, making it more susceptible to attack. This innovative combination could offer a more targeted and effective approach to treating ovarian cancer.

What evidence suggests that genetically modified T cells and decitabine could be effective for ovarian cancer?

In this trial, participants will receive a combination of specially modified T cells and a drug called decitabine to treat ovarian cancer. Decitabine increases a protein called NY-ESO-1 on cancer cells, making them easier for the modified T cells to find and attack. These T cells target and destroy cells with the NY-ESO-1 protein. Studies have found that this combination can enhance the body's immune response against tumors. In some cases, patients developed strong immune cells that effectively attacked and eliminated cancer cells. This suggests that the treatment could be effective against ovarian and related cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Emese Zsiros

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or refractory ovarian, primary peritoneal, or fallopian tube cancer. Participants must have HLA-A*02;01 positivity, good performance status (ECOG 0-1), life expectancy over 4 months, adequate organ function and blood counts, measurable disease by irRECIST criteria, and be at least 4 weeks out from prior treatments. Women of childbearing potential must agree to use effective contraception.

Inclusion Criteria

Leukocytes >= 3 x 10^9/L

I agree to use effective birth control methods during and after the study for several years.

Total bilirubin within normal institutional limits

Exclusion Criteria

Lack of availability of a patient for immunological and clinical follow-up assessment

I do not have any ongoing illnesses or social situations that would prevent me from following the study's requirements.

I do not have active hepatitis C or have a recent test showing I'm clear of it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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, followed by low-dose IL-2 for 2 weeks from Day 1 to Day 14.

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Monthly at 3-9 months, every 6 months for 4 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Genetically Engineered NY-ESO-1-specific T Lymphocytes

Trial Overview The trial is testing the safety of genetically modified T cells designed to target NY-ESO-1 protein on tumor cells combined with Decitabine in patients whose cancer has returned or hasn't responded to treatment. Patients' own T cells are collected and engineered before being reintroduced into their body alongside Decitabine to potentially enhance the immune response against cancer.

How Is the Trial Designed?

Group I: Treatment (decitabine, genetically modified T cells) Experimental Treatment 5 Interventions

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..

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5844797/

NY-ESO-1 Vaccination in Combination with Decitabine ... We show that 1) a majority of patients develop NY-ESO-1 specific CD4+ and CD8+ T-lymphocyte responses; 2) these NY-ESO-1-specific T-lymphocytes can recognize ...

2. clinicaltrial.be clinicaltrial.be/en/details/9404?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Genetically Modified T Cells and Decitabine in Treating P... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9568428/

Decitabine enhances targeting of AML cells by NY-ESO-1 ... The combination of DAC with NY-ESO-1-specific dTCR-T cells showed a superior anti-tumor efficacy in vivo and prolonged the survival of an AML ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/24/5/1019/81149/NY-ESO-1-Vaccination-in-Combination-with

NY-ESO-1 Vaccination in Combination with Decitabine ... Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 ...

5. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04073-y

Treatment with decitabine induces the expression of stemness ... We conclude that the upregulation of both stemness and immune checkpoint markers by DAC treatment on CRC cells might represent a mechanism of immune evasion.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5599090/

The safety, efficacy, and treatment outcomes of a combination ... This trial tested the safety, efficacy, and treatment outcomes of decitabine-based chemotherapy or combined with immunotherapy in recurrent ovarian cancer ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28932630/

The safety, efficacy, and treatment outcomes of a ... This trial tested the safety, efficacy, and treatment outcomes of decitabine-based chemotherapy or combined with immunotherapy in recurrent ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03467178

NCT03467178 | Study on Decitabine Plus Carboplatin ... This is an open-label, prospective, multicenter, randomized Phase II, clinical trial evaluating the efficacy and safety of Decitabine-Carboplatin combination

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304419X23002159

Research progress of decitabine in the treatment of solid ... In a meta-analysis conducted by Miriam et al., decitabine monotherapy resulted in a reported response rate of 40% [95% CI, 32–48%] in AML, with a median overall ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7037

Phase 2 study of ASTX727 (cedazuridine/decitabine) plus ... Grade 3 or higher adverse events directly attributable to therapy were mainly myelosuppression-related and included neutropenic infections in 3 ...