Immunotherapy for Solid Cancers

(REST Trial)

Not currently recruiting at 1 trial location

Overseen By Fahmida Hoq, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: Steroids, ATG, Campath

Disqualifiers: Uncontrolled infections, Active HIV, GVHD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment for individuals with high-risk solid tumors that haven't responded to standard treatments or have returned after treatment. The goal is to determine if a special immune cell infusion, called Tumor Associated Antigen Lymphocytes (TAA-CTL), can safely help the body combat these challenging cancers, such as Ewing sarcoma or esophageal carcinoma. Researchers are studying two groups: one includes patients who have undergone a specific type of stem cell transplant, and the other includes those who have not. Suitable candidates have a diagnosed high-risk solid tumor that either didn't respond to regular treatment or has recurred after treatment. 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 new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on steroids, the dose must be less than 0.5 mg/kg/day of prednisone (or equivalent). Also, you should not have received certain immunosuppressive treatments like ATG or Campath within 28 days before the cell infusion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a type of immune cell called TAA-CTL has been studied for its safety in treating solid tumors. In earlier studies, patients have tolerated these special cells well. Reports suggest they might offer a non-toxic treatment option for tumors that have returned or are difficult to treat.

One study found that TAA-CTLs could safely help patients live longer with these challenging conditions. Patients did not experience severe side effects from this treatment, making it a promising option for those whose tumors do not respond to other treatments.

Overall, while more research is needed, early findings suggest that TAA-CTLs are safe and could be effective for treating high-risk solid tumors. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for solid cancers?

Researchers are excited about tumor-associated antigen lymphocytes (TAA-CTL) because they offer a targeted approach to treating solid cancers. Unlike traditional therapies like chemotherapy and radiation, which attack all rapidly dividing cells, TAA-CTL specifically targets cancer cells by recognizing unique markers on their surface. This precision can potentially reduce side effects and improve effectiveness. Additionally, TAA-CTL can be infused after a patient has undergone either a stem cell transplant or conventional therapy, providing flexibility in treatment plans. This innovative approach represents a significant step forward in cancer immunotherapy.

What evidence suggests that this treatment might be an effective treatment for solid cancers?

Research has shown that a type of immune cell treatment, called TAA-CTL, may effectively treat solid tumors. In previous studies, 73% of patients treated with these cells experienced a halt in cancer growth for at least six months. This indicates that most patients had a pause in cancer progression during this period. Additionally, about 75% of patients with aggressive or recurring cancer achieved some level of disease control after receiving this treatment. In this trial, participants in Group A, who have undergone an allogeneic hematopoietic stem cell transplant, and participants in Group B, who have received conventional therapy, will receive TAA-CTLs. These results suggest that TAA-CTLs could offer new hope for people with difficult-to-treat cancers. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people aged 6 months to 60 years with high-risk solid tumors like Ewing sarcoma or adenocarcinoma, who have either not responded to standard treatments or whose cancer has returned. Participants need a minimum level of immune cells and organ function, must not be pregnant or breastfeeding, agree to use contraception if applicable, and cannot have uncontrolled infections or recent immunotherapy.

Inclusion Criteria

I (or my guardian) can understand and agree to the study's terms.

Bilirubin ≤ 2.5 mg/dL

Absolute lymphocyte count (ALC) greater than 1000/µL

Exclusion Criteria

I do not have any infections that are currently uncontrolled.

Patients with active HIV

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAA-CTL infusions with dose escalation to determine the maximum tolerated dose

Approximately 6 months

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extension

Participants with stable disease or better may receive additional doses of CTLs at 28-day intervals

Up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Tumor associated antigen lymphocytes (TAA-CTL)

Trial Overview The study tests the safety and potential effectiveness of TAA-CTLs—immune cells trained to target multiple tumor-associated antigens—in patients with tough-to-treat solid tumors. The goal is to see if these specialized T cells can help fight off cancers that haven't responded well to other treatments.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 1 Intervention

Group B includes patients who have undergone conventional (standard) therapy which does not include an allogeneic HSCT. Within group B, a cohort of patients with relapsed or refractory Wilms tumor will be enrolled and receive a lymphodepleting chemotherapy regimen followed by TAA-T. Group B patients (no prior allogeneic HSCT): TAA-T will be infused any time \>1 week after completing most recent course of conventional (non-investigational) therapy for their disease. Patients receiving lymphodepletion will be \>2 weeks from most recent course of conventional therapy and have nadired and recovered before beginning protocol therapy.

Group II: Group A Experimental Treatment 1 Intervention

Group A includes patients who have undergone an allogeneic hematopoietic stem cell transplant (HSCT) as part of their prior therapy. Group A patients (post allogeneic HSCT): TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Published Research Related to This Trial

MDM2-specific T cells can survive in the body despite being exposed to normal tissue expression, but they struggle to proliferate and function effectively, leading to high rates of cell death when stimulated by their target antigen.

Cytokines like IL-2 and IL-15 can help improve the survival and function of these T cells, but they do not restore their full effectiveness, indicating potential challenges for immunotherapy targeting common tumor-associated antigens like MDM2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of T cell tolerance to the tumor-associated antigen MDM2: cytokines can restore antigen responsiveness, but not high avidity T cell function. Bendle, GM., Xue, SA., Holler, A., et al.[2022]

Recombinant monoclonal antibodies (MAbs) are becoming important in cancer therapy, especially when used alongside traditional anti-cancer drugs, enhancing treatment effectiveness.

Combining antibody therapy with toxins or radioisotopes, and developing immune cells like cytotoxic T-lymphocytes (CTLs) or natural killer (NK) cells that target tumor-associated antigens (TAAs), could significantly improve cancer immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible applications of antibodies or their genes in cancer therapy. Kuroki, M., Huang, J., Shibaguchi, H., et al.[2007]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

In a study involving 12 chronic lymphocytic leukemia (CLL) patients, MDM2-specific T cells were successfully generated in 7 patients, demonstrating the potential of MDM2 as a tumor-associated antigen for immunotherapy.

The study found that the ability of antigen-presenting cells (APCs) to secrete IFN-gamma was a key factor in generating effective MDM2-specific T cells, highlighting the importance of APC functionality in developing targeted immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes. Mayr, C., Bund, D., Schlee, M., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482274/

Novel tumor-infiltrating lymphocytes therapy in solid tumors Median overall survival (OS) was 13.9 months, with a 5-year OS rate of 19.7%. Treatment-emergent adverse events (TEAEs) were predominantly ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31356143/

Immunotherapy of Relapsed and Refractory Solid Tumors ... Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02239861

TAA-Specific CTLS for Solid Tumors (TACTASOM) This is a clinical trial for patients with a solid tumor which has come back, or may come back, or has not gone away after treatment, including the standard ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825000599

Outcomes of tumor-infiltrating lymphocyte therapy in solid ... TIL therapy is effective in treating solid tumors, especially melanoma, but its results vary according to the kind of cancer as well as tumour ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.3042

Ex vivo expanded multi-antigen specific lymphocytes for ... Despite aggressive and multiply relapsed disease, 75% of patients have demonstrated evidence of disease control after TAA-T with epitope ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02239861

TAA-Specific CTLS for Solid Tumors (TACTASOM) This is a study using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy. The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05238792

NCT05238792 | Multi Tumor-Associated Antigen-Specific T ... This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10972864/

Adoptive T cell therapy for solid tumors - PubMed Central - NIH In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell ...