NK Cell Therapy + Chemotherapy for Sarcoma
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Steroids, Immunosuppressants, Anticancer agents
Disqualifiers: Infections, Hepatitis, HIV, Autoimmune, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
The goal of this clinical research study is to find a recommended dose of donated NK cells that can be given along with chemotherapy to patients with advanced cancers. The safety and effects of this therapy will also be studied.
Do I need to stop my current medications to join the trial?
The trial requires that you stop taking certain medications before starting. You must be at least 2 weeks from your last chemotherapy and stop any tyrosine kinase inhibitors or targeted therapies at least 3 days before starting the trial's chemotherapy. If you're on systemic steroids, you may need to adjust your dose.
What data supports the effectiveness of the treatment NK Cell Therapy + Chemotherapy for Sarcoma?
Research shows that T-cell therapies targeting NY-ESO-1, a protein found in some sarcomas, have been effective in treating advanced soft tissue sarcomas. In a clinical trial, patients receiving a similar treatment had a 41.7% response rate, with a median progression-free survival of 7.2 months.12345
Is NK Cell Therapy + Chemotherapy for Sarcoma safe for humans?
Research shows that treatments involving NY-ESO-1-specific TCR T cells, combined with chemotherapy drugs like cyclophosphamide and fludarabine, have been tested in humans with advanced soft tissue sarcoma. These studies found no serious treatment-related side effects, indicating that the therapy is generally safe.13456
What makes the NK Cell Therapy + Chemotherapy for Sarcoma treatment unique?
This treatment is unique because it combines NK (natural killer) cells engineered to target the NY-ESO-1 protein, which is often found in sarcoma cells, with chemotherapy. This approach leverages the body's immune system to specifically attack cancer cells, potentially offering a more targeted and effective treatment compared to traditional therapies.36789
Eligibility Criteria
This trial is for people aged 16-80 with advanced sarcomas, specifically synovial or myxoid/round cell liposarcoma, who've tried at least one standard treatment without success. They must have proper liver, kidney, heart, and blood function and no serious infections or autoimmune diseases. Participants need to be HLA-A*02 positive with NY-ESO-1 expression in tumors.Inclusion Criteria
My organs are functioning well according to my recent tests.
My cancer expresses NY-ESO-1 and I have specific HLA types.
My cancer is either synovial sarcoma or myxoid/round cell liposarcoma, tests positive for specific HLA types, and shows high NY-ESO-1 expression.
See 25 more
Exclusion Criteria
- Uncontrolled arrhythmia, considered per PI
I have an active neurological disorder.
I have serious side effects from past cancer treatment.
See 14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Lymphodepleting Chemotherapy
Participants receive lymphodepleting chemotherapy prior to NK cell infusion
1-2 weeks
Treatment
Participants receive adoptive NK cells expressing an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1
4-6 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Cyclophosphamide (Alkylating agents)
- Fludarabine phosphate (Anti-metabolites)
- NY-ESO-1 TCR/IL-15 NK (CAR T-cell Therapy)
Trial OverviewThe study tests the safety and optimal dose of donated NK cells expressing a TCR against NY-ESO-1 combined with chemotherapy (Cyclophosphamide and Fludarabine phosphate) in patients with specific advanced cancers to see how well they tolerate it and its effects on their disease.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Dose escalation - Inpatient and OutpatientExperimental Treatment3 Interventions
Participants will be assigned to receive a dose level of NK cells based on when the participants joins the study. Up to 6 participants will be enrolled at each dose level. If no intolerable side effects are seen after the first 3-6, the next group of participants will get at higher dose. Up to 4 dose levels of NK cells will be tested. If the first dosing group shows intolerable side effects, a lower dose will be tested.
NY-ESO-1 TCR/IL-15 NK is already approved in United States for the following indications:
🇺🇸 Approved in United States as NY-ESO-1 TCR/IL-15 NK for:
- Multiple Myeloma
- Synovial Sarcoma
- Myxoid/Round Cell Liposarcoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Safety and Efficacy of NY-ESO-1 Antigen-specific T-cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial. [2023]To determine, for patients with advanced or recurrent synovial sarcoma not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor gene and siRNAs to inhibit the expression of endogenous T-cell receptors (product code: TBI-1301).
Histological Assessment of Synovial Sarcoma Before and After TCR-T Cell Therapy and Cryoablation: A Case Report. [2023]Cancer/testis antigens (CTAs) are well-known molecular targets with expression restricted to testicular germ cells and malignant tumors. T-cell receptor (TCR)-engineered T-cell (TCR-T) therapy against CTAs in patients with sarcoma has shown substantial progress, but resistance to TCR-T therapy remains a critical problem. In this report, we present a case of synovial sarcoma treated with TCR-T therapy targeting the New York-esophageal squamous cell carcinoma (NY-ESO)-1 protein. Histological findings were compared before and after TCR-T therapy and before and immediately after cryoablation.
Pushing forward in sarcoma with a new TCR targeting NY-ESO-1. [2023]A phase 1 trial demonstrating the safety and efficacy of a novel NY-ESO-1-specific TCR-T cells by Pan et al.1 is a major step forward for adoptive T cell therapy in the clinical practice of advanced soft tissue sarcomas.
Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma. [2023]New York esophageal squamous cell carcinoma-1 (NY-ESO-1)-specific T cell receptor (TCR) T cell therapy is effective in tumors with NY-ESO-1 expression, but a safe and effective TCR-T cell therapeutic protocol remains to be improved. Here, we report a phase 1 investigational new drug clinical trial with TCR affinity-enhanced specific T cell therapy (TAEST16001) for targeting NY-ESO-1. Enrolled patients receive TAEST16001 cell infusion after dose-reduced lymphodepletion with cyclophosphamide (15 mg/kg/day × 3 days) combined with fludarabine (20 mg/m2/day × 3 days), and the TCR-T cells are maintained with low doses of interleukin-2 injection post-adoptive transfer. Analysis of 12 patients treated with the regimen demonstrates no treatment-related serious adverse events. The overall response rate is 41.7%. The median progression-free survival is 7.2 months, and the median duration of response is 13.1 months. The protocol of TAEST16001 cells delivers a safe and highly effective treatment for patients with advanced soft tissue sarcoma (ClinicalTrials.gov: NCT04318964).
IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy. [2022]Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.
A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab. [2023]Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.
Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma. [2022]Sarcomas are a heterogeneous group of mesenchymal neoplasms, many of which are associated with a high risk of metastasis and poor prognosis. Conventional chemotherapy and targeted therapies have varying effects across individuals and tumour subtypes. The current therapies frequently provide limited clinical benefit; hence, more effective treatments are urgently needed. Recent advances in immunotherapy, such as checkpoint inhibition or adoptive cell therapy (ACT), show potential in increasing efficacy by providing a more personalized treatment. Therapy with tumour-infiltrating lymphocytes (TILs) is an emerging field in immunotherapy. Here, we collected 190 sarcoma tumour specimens from patients without pre-operative adjuvant treatment in order to isolate TILs. We compared different methods of TIL expansion and optimized a protocol specifically for efficacy in culturing TILs from sarcoma. The expanded TIL populations were characterized by flow cytometry analysis using CD3, CD4, CD8, CD14, CD19 and CD56 markers. The TIL populations were non-specifically stimulated to establish TIL reactivity. Through an optimized expansion protocol, TILs were isolated and cultured from 54 of 92 primary sarcoma specimens. The isolated TILs varied in CD4+ and CD8+ T-cell compositions and retained their ability to release IFNγ upon stimulation. Our results suggest that certain sarcoma subtypes have the potential to yield a sufficient number of TILs for TIL therapy.
NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways. [2021]Ewing sarcoma (EWS) is a malignant bone-associated sarcoma, with poor prognosis in case of metastasis or relapse. To explore the feasibility of natural killer (NK) cell mediated immunotherapy and to identify molecular mechanisms involved, the susceptibility of EWS to NK cells was investigated.
HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma. [2022]Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS.