~8 spots leftby Sep 2025

attIL12 T-Cell Therapy for Sarcoma

Recruiting in Palo Alto (17 mi)
J. Andrew Livingston | MD Anderson ...
Overseen byJohn A Livingston, MD MS
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Corticosteroids
Disqualifiers: Autoimmune disease, CNS metastases, others
No Placebo Group
Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment that uses specially modified immune cells combined with a drug to help fight advanced or hard-to-treat soft tissue and bone cancers. The goal is to see if this approach can safely control the disease in patients who have not responded well to other treatments.

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

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment at the time of leukapheresis or attIL12 T cell infusion. Standard of care anti-cancer therapy is allowed after leukapheresis but before starting cyclophosphamide. Non-cancer-related medications like insulin for diabetes are acceptable.

What data supports the idea that attIL12 T-Cell Therapy for Sarcoma is an effective treatment?

The available research shows that while attIL12 T-Cell Therapy for Sarcoma is a promising approach, there is limited direct evidence of its effectiveness specifically for sarcoma. However, other similar T-cell therapies, like CAR-T cell therapy, have shown encouraging results in treating sarcomas by targeting specific antigens associated with the cancer. These therapies have been successful in other cancers, suggesting potential for sarcoma treatment. Additionally, the research on tumor-infiltrating lymphocytes (TILs) indicates that certain sarcoma subtypes can yield enough TILs for therapy, which may support the effectiveness of T-cell-based treatments like attIL12.12345

What safety data is available for attIL12 T-Cell Therapy for Sarcoma?

The safety data for attIL12 T-Cell Therapy, which may be related to other engineered T-cell therapies like CAR-T and TCR-T cells, indicates that while these therapies show promise in treating cancer, they are associated with significant toxicities. These include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and on-target off-tumor effects. Preclinical studies in mice have shown no acute toxicity or immunotoxicity for TCRα-transduced T cells, suggesting a favorable safety profile. However, clinical trials have reported significant toxicity related to antigen expression on normal tissues. Efforts are ongoing to improve safety measures, such as the use of inducible safety switches, to mitigate these risks.678910

Is attIL12 T-Cell Therapy a promising treatment for sarcoma?

Yes, attIL12 T-Cell Therapy is a promising treatment for sarcoma. It is part of a new wave of immunotherapies that use the body's own immune cells to fight cancer. This approach has shown potential in increasing the effectiveness of treatment by targeting specific cancer cells, which could lead to better outcomes for patients with sarcoma.1351112

Research Team

J. Andrew Livingston | MD Anderson ...

John A Livingston, MD MS

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people aged 12 and older with advanced or metastatic soft tissue or bone sarcoma, who have tried at least one systemic therapy unless none exist for their subtype. They must be in good physical condition (ECOG status of 0 or 1), not pregnant, willing to use contraception, and have proper organ function. Exclusions include active infections like hepatitis B/C, autoimmune diseases within the past two years, untreated brain metastases, recent major surgery, HIV/AIDS, other cancer treatments ongoing or a second active malignancy.

Inclusion Criteria

My osteosarcoma cannot be surgically removed and has come back or spread.
Measurable disease according to RECIST 1.1
I am 12 years old or older.
See 10 more

Exclusion Criteria

Active or prior documented autoimmune disease within the past 2 years
I have not received a live vaccine in the last 28 days.
I have had a primary immunodeficiency, organ transplant, or tuberculosis.
See 11 more

Treatment Details

Interventions

  • attIL2-T cells (CAR T-cell Therapy)
  • Cyclophosphamide (Alkylating agents)
Trial OverviewThe trial is testing attIL2-T cell therapy combined with Cyclophosphamide in patients with soft tissue or bone sarcomas. The goal is to determine a safe dosage that can control the disease. Participants will receive T-cells designed to target tumor cells directly.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Part B: Osteosarcoma Dose ExpansionExperimental Treatment2 Interventions
Participants will receive attIL2-T cell therapy at the recommended dose that was found in Phase 1.
Group II: Part A: Dose Findings (MTD)Experimental Treatment2 Interventions
The dose of attIL2-T cell therapy the participants will receive will depend on when the participants joined this study. The first group of participants will receive the lowest dose level of attIL2-T cell therapy.

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3107
Patients Recruited
1,813,000+

Findings from Research

In a study involving three adult T cell leukemia/lymphoma (ATL) patients, expanded Tax-specific CTLs showed significant therapeutic potential in NOG mice, leading to increased infiltration of CD8-positive T cells into ATL lesions and a notable decrease in ATL cell presence in the blood, spleen, and liver.
The treatment with Tax-CTL not only prolonged survival in some ATL/NOG mice but also demonstrated varying efficacy based on the patient's disease type, marking the first report of adoptive therapy with antigen-specific CTLs resulting in antitumor effects in vivo.
Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model.Masaki, A., Ishida, T., Suzuki, S., et al.[2013]
The phase 1 trial showed that NY-ESO-1-specific TCR-T cells are both safe and effective for treating advanced soft tissue sarcomas, marking a significant advancement in adoptive T cell therapy.
This study represents an important step in the clinical application of T cell therapies, potentially offering new hope for patients with this challenging type of cancer.
Pushing forward in sarcoma with a new TCR targeting NY-ESO-1.Al-Marayaty, R., Pollack, SM.[2023]
Modified T-cell therapies, particularly those targeting cancer testis antigens like NY-ESO-1, show promising efficacy in treating sarcomas, with response rates of up to 60% observed in clinical trials for specific types like synovial sarcoma.
Challenges remain in the form of HLA-restriction and non-immunogenic tumor microenvironments, which may limit the effectiveness of these therapies, highlighting the need for further development to enhance T-cell specificity and persistence.
Immunotherapy of sarcomas with modified T cells.Mahalingam, P., Julve, M., Huang, P., et al.[2023]
Liposomal avasimibe was successfully attached to T cells, enhancing their activation and antitumor efficacy without disrupting their normal functions, leading to significant improvements in treating solid tumors like melanoma and glioblastoma in mouse models.
The engineered T cells demonstrated a strong safety profile, with no significant systemic side effects observed, and showed remarkable effectiveness, completely eradicating glioblastoma in 3 out of 5 treated mice.
Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy.Hao, M., Hou, S., Li, W., et al.[2022]
In a study using murine sarcomas, T lymphocytes from tumor-draining lymph nodes were successfully activated in vitro with anti-TCR monoclonal antibodies and interleukin-2, leading to an eightfold increase in cell numbers and significant reduction of established pulmonary metastases.
The activated T cells demonstrated tumor-specific therapeutic efficacy, resulting in prolonged survival for treated mice, with 30% remaining tumor-free for over 90 days, indicating the potential for long-lasting systemic immunity against the tumor.
Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph node cells.Mitsuma, S., Yoshizawa, H., Ito, K., et al.[2018]
Researchers developed stable T cell clones from patients with osteogenic sarcoma and malignant fibrohistiocytoma that specifically target and kill autologous tumor cells, demonstrating their potential for personalized cancer immunotherapy.
These T cell clones maintained their cytotoxic activity for over 6 months and recognized a common sarcoma-associated antigen, indicating a promising mechanism for targeting tumors while sparing normal cells.
Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity.Slovin, SF., Lackman, RD., Ferrone, S., et al.[2018]

References

Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma. [2022]
Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model. [2013]
Pushing forward in sarcoma with a new TCR targeting NY-ESO-1. [2023]
Immunotherapy of sarcomas with modified T cells. [2023]
Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. [2020]
Improving the efficacy and safety of engineered T cell therapy for cancer. [2020]
Development of adoptive cell therapy for cancer: a clinical perspective. [2021]
Safety evaluation of the mouse TCRα - transduced T cell product in preclinical models in vivo and in vitro. [2022]
Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Building safety into CAR-T therapy. [2023]
Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph node cells. [2018]
12.United Statespubmed.ncbi.nlm.nih.gov
Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity. [2018]