40 Participants Needed

attIL12 T-Cell Therapy for Sarcoma

JL
Overseen ByJohn Livingston, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

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.

Will I have to stop taking my current medications?

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. You can continue using hormones for non-cancer-related conditions like insulin for diabetes.

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 data supports the effectiveness of the attIL12 T-Cell Therapy treatment for sarcoma?

Research shows that modified T-cell therapies, like CAR-T cell therapy, have shown promise in treating other cancers and are being explored for sarcomas. Additionally, therapies using tumor-infiltrating lymphocytes (TILs) have potential in sarcoma treatment, as certain sarcoma subtypes can yield enough TILs for therapy, suggesting a personalized approach could be effective.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 generally safe for humans?

Research on similar T-cell therapies shows that while they can be effective against cancer, they may also cause significant side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). However, some studies have shown no obvious systemic side effects, indicating that safety can vary depending on the specific therapy and its application.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

What makes attIL12 T-Cell Therapy unique for treating sarcoma?

attIL12 T-Cell Therapy is unique because it involves genetically modifying T-cells to express IL-12, a protein that boosts the immune response, directly on their surface, which may enhance their ability to target and destroy cancer cells in sarcoma. This approach is different from traditional treatments as it aims to harness and amplify the body's own immune system to fight the cancer more effectively.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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive attIL12-T cell therapy in combination with cyclophosphamide to determine safety and efficacy

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

Treatment Details

Interventions

  • attIL2-T cells
  • Cyclophosphamide
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.

attIL2-T cells is already approved in United States for the following indications:

🇺🇸
Approved in United States as attIL12-T cells for:
  • Advanced/Metastatic Soft Tissue Sarcoma
  • Bone Sarcoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Findings from Research

In a study involving 190 sarcoma tumor specimens, researchers successfully isolated tumor-infiltrating lymphocytes (TILs) from 54 of 92 primary sarcoma samples, indicating that certain sarcoma subtypes can provide enough TILs for potential immunotherapy.
The optimized protocol for expanding TILs demonstrated that these cells retained their ability to react and release IFNγ upon stimulation, suggesting their viability for future personalized immunotherapy treatments in sarcoma patients.
Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma.Ko, A., Coward, VS., Gokgoz, N., et al.[2022]
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]

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]