ALI Post Radiation Therapy for Thoracic Cancers

Overseen By Gheath Al-Atrash

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Prior chest radiotherapy, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of using a patient's own immune cells, known as autologous lymphocyte infusions (ALI), for treating non-small cell lung cancer or esophageal cancer. The study targets patients already receiving chemotherapy and radiation therapy for these cancers. Participants diagnosed with these specific cancers and undergoing chemoradiation might be suitable candidates. The goal is to determine if this new treatment can enhance the body’s natural defenses against cancer. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, any systemic therapy (treatment affecting the whole body) aside from standard immunotherapy should not be planned for at least 6 weeks after the autologous lymphocyte infusion.

Is there any evidence suggesting that autologous lymphocyte infusion is likely to be safe for humans?

Studies have shown that using a person's own immune cells, known as autologous lymphocyte infusion (ALI), is safe and feasible for patients with chest cancers, such as lung and esophageal cancer, after completing chemotherapy and radiation. Earlier research tested ALI and found it well-tolerated, with most patients experiencing no severe side effects.

The treatment aims to strengthen the immune system, and early trials have shown positive results. However, while initial findings are promising, further research is necessary to fully confirm its safety and effectiveness. Current evidence considers ALI a safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for thoracic cancers, which often include chemotherapy, radiation, or targeted therapies, autologous lymphocyte infusion (ALI) uses the patient's own immune cells. Researchers are excited about ALI because it harnesses the body's own lymphocytes, collected through a process called apheresis, and reinfuses them after radiation therapy. This approach may enhance the body's natural ability to fight cancer, offering a potentially safer and more personalized treatment option. Additionally, since ALI uses un-manipulated cells from the patient, it reduces the risk of rejection or severe side effects that can occur with other immunotherapy treatments.

What evidence suggests that autologous lymphocyte infusion might be an effective treatment for non-small cell lung cancer or esophageal cancer?

Research has shown that certain immune cells, called tumor-infiltrating lymphocytes (TIL), can recognize and destroy cancer cells in lung cancer. These cells resemble those used in autologous lymphocyte infusion (ALI), a treatment under study in this trial. ALI involves collecting a patient's own immune cells and reintroducing them into the body after chemotherapy and radiation. This process is believed to aid the immune system in recovering and fighting cancer more effectively. Previous studies have demonstrated that ALI is safe and can increase white blood cell counts. Evidence also indicates that TIL therapy, which is similar, effectively treats non-small cell lung cancer and other solid tumors. These findings suggest ALI may be a promising treatment option. ^{1 2 5 6 7}

Who Is on the Research Team?

Gheath Al-Atrash

Principal Investigator

MD Anderson Cancer Center, Houston, Texas

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-small cell lung cancer or esophageal cancer at stages II-IVA, where chemoradiation is standard. Participants must not have had prior chest radiotherapy, any systemic therapy other than standard immunotherapy before 6 weeks after ALI, be pregnant, or have a life expectancy under 6 months.

Inclusion Criteria

My lung or esophageal cancer is at a stage where combined chemotherapy and radiation is recommended.

Exclusion Criteria

Pregnancy

I will not start any new systemic treatments other than standard immunotherapy within 6 weeks after ALI.

I have had radiation therapy to my chest before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation/Chemoradiation

Participants undergo radiation or chemoradiation therapy as part of their cancer treatment

6 weeks

Autologous Lymphocyte Infusion (ALI)

Participants receive autologous lymphocyte infusions to improve lymphocyte counts after radiation/chemoradiation

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Autologous lymphocyte infusion (ALI)

Trial Overview The study tests the safety and effectiveness of autologous lymphocyte infusion (ALI) in patients receiving chemotherapy and radiation for lung or esophageal cancer. It aims to understand if this approach improves treatment outcomes.

How Is the Trial Designed?

Group I: Treatment (Autologous Lymphocyte Infusions) Experimental Treatment 1 Intervention

The purpose of this study is to determine the safety and preliminary efficacy of un-manipulated autologous lymphocyte infusion (ALI) using the patient's own lymphocytes collected using apheresis, and infused after the completion of radiation/chemoradiation.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 786 patients with non-small cell lung cancer, a lower effective dose to immune cells (EDIC) was linked to better progression-free survival (PFS) and overall survival (OS), indicating that minimizing EDIC could improve treatment outcomes.

Higher EDIC levels (≥4.7 Gy) were associated with increased risks of severe lymphopenia and treatment-related toxicities, such as pneumonitis and unplanned hospitalizations, suggesting that strategies like proton therapy, which results in lower EDIC, may enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC. Friedes, C., Iocolano, M., Lee, SH., et al.[2023]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

In a study of 109 advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), 50.5% experienced immune-related adverse events (irAEs), with baseline levels of CD8+ T lymphocytes identified as a significant predictor for these events.

Higher baseline CD8+ T lymphocyte levels not only correlated with an increased risk of irAEs but also indicated better clinical outcomes, with longer progression-free survival (PFS) and overall survival (OS) in patients who experienced irAEs compared to those with lower levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive Correlation of Peripheral CD8+ T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors. Wu, K., Xia, B., Zhang, J., et al.[2023]

In a study involving 70 samples from patients with advanced non-small cell lung carcinoma (NSCLC), 46 samples of tumor-infiltrating lymphocytes (TIL) were successfully expanded in vitro, producing between 10 to 50 billion cells that effectively targeted and killed the patients' own cancer cells.

The TILs showed a preselected oligoclonal population that could be expanded while retaining their cancer-fighting properties, suggesting a promising approach for adoptive immunotherapy in patients with residual NSCLC after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterisation for their use in adoptive immunotherapy. Melioli, G., Ratto, G., Guastella, M., et al.[2019]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625035291

Phase II Trial of Autologous Lymphocyte Infusions after ... We hypothesized that autologous lymphocyte infusions (ALI) following thoracic chemoradiation (CRT) would be feasible, safe, and facilitate immune reconstitution ...

2. withpower.com withpower.com/trial/ali-post-radiation-therapy-for-thoracic-cancers-42fb0

ALI Post Radiation Therapy for Thoracic Cancers Research shows that tumor infiltrating lymphocytes (TIL), which are similar to the cells used in ALI, can recognize and destroy cancer cells in lung cancer.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-07836

Autologous Lymphocyte Infusions after Chemotherapy and/ ... This phase II trial studies the effect of autologous lymphocyte infusions after standard of care chemotherapy and/or radiation therapy on white blood cell count

4. clinicaltrial.be clinicaltrial.be/fr/details/49760?per_page=100&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_eligible=0&only_active=0

ALI Post Radiation Therapy in Patients With Lung and Esop... The purpose of this study is to determine the safety and preliminary efficacy of un-manipulated autologous lymphocyte infusion (ALI) using ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10840042/

Efficacy and safety of autologous tumor-infiltrating ... Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06519669

Autologous Tumor-Infiltrating Lymphocyte Injection(GT201) ... This study is a single arm, open design aimed at evaluating the safety and tolerability of Autologous Tumor-Infiltrating Lymphocyte (GT201 injection ) for ...

7. redjournal.org redjournal.org/article/S0360-3016(25)03529-1/fulltext

Phase II Trial of Autologous Lymphocyte Infusions after ... ALI is safe and feasible after definitive CRT for patients with thoracic cancers. Future studies are needed to assess the quality of immune ...