Cell Therapy for Kidney Cancer

KE
KG
Overseen ByKristen Gunn E Wood, R.N.
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Must be taking: Antiangiogenics, Immune-checkpoint inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called gene transfer for kidney cancer. The process involves taking a person's white blood cells, modifying them in a lab to attack cancer cells, and then reintroducing them into the body to assess tumor shrinkage and safety. Known as cell infusion (a type of cell therapy), this treatment targets individuals with certain types of kidney cancer that have progressed despite previous treatments. Participants will undergo several procedures, including blood cell collection and hospital stays for treatment and recovery. Ideal candidates have been diagnosed with specific kidney cancer, have experienced disease progression, and can tolerate a hospital stay. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 had certain cancer treatments like anti-VEGFR therapy or mTOR inhibitors for at least 7 days before the T-cell infusion, and PD-1/PD-L1 or CTLA-4 inhibitors for 4 weeks before the infusion.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a new gene therapy using modified T-cells, called HERV-E TCR transduced T-cells, has been tested in people with kidney cancer. In one study, patients with advanced kidney cancer received these specially altered T-cells along with a moderate dose of IL-2, a drug that helps the T-cells survive and function better.

The study aimed to understand the side effects of this treatment. Some patients experienced side effects, but they were generally manageable. For instance, IL-2 can cause flu-like symptoms, such as fever and chills, in some patients. However, there were no reports of severe or life-threatening issues directly linked to the T-cell treatment.

This trial is in its early stages, focusing mainly on safety. Early trials usually involve small groups of people to closely monitor any risks. Until more information becomes available, participants should discuss the potential risks and benefits with their doctors.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the cell therapy for metastatic clear cell renal cell carcinoma because it represents a novel approach that differs significantly from standard treatments like targeted therapy, immunotherapy, and surgery. Unlike these conventional methods, this therapy involves the infusion of genetically modified T-cells that are engineered to target and attack cancer cells more precisely. The treatment uses HERV-E TCR transduced CD8+/CD34+ enriched T-cells, which are a new type of engineered immune cell designed to enhance the body's natural ability to fight cancer. This targeted action could potentially lead to more effective tumor eradication with fewer side effects. Additionally, the use of IL-2 to boost the immune response after cell infusion offers another layer of innovation, potentially improving treatment outcomes.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that a new type of modified immune cell, called HERV-E TCR transduced T-cells, may help treat kidney cancer, particularly clear cell renal cell carcinoma. In earlier studies, researchers designed these modified cells to find and destroy cancer cells by recognizing a specific protein on the tumor. Early results suggested that this method can shrink tumors. In this trial, participants will receive varying levels of HERV-E TCR transduced T-cells to evaluate their effectiveness. Although more research is needed, these initial findings offer hope for a new way to combat this cancer.23456

Who Is on the Research Team?

RW

Richard W Childs, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

Adults aged 18-75 with certain types of kidney cancer, who have tried at least one antiangiogenic drug and an immune-checkpoint inhibitor. They must not be HIV or hepatitis positive, have a life expectancy over 3 months, agree to use contraception, and have someone to care for them during the first month post-treatment.

Inclusion Criteria

Patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 180 days (female patients) or 90 days (male patients) after the end of the treatment if sexually active and able to bear or beget children. In addition, male patients must refrain from sperm donation for 90 days after the final dose of investigational product. Female patients must refrain from egg cell donation for 180 days after the final dose of investigational product.
I have been treated with drugs that target blood vessel growth and immune system checkpoints, unless I couldn't for health, availability, or personal reasons.
I have someone who can stay with me during the first month of my treatment.
See 12 more

Exclusion Criteria

I have had a severe reaction to immunotherapy that needed long-term treatment, but not for vitiligo or hypothyroidism.
I have clear cell RCC and no other cancer needing treatment in the last 4 years, except for certain skin, cervical, or breast cancers.
I can understand the study details and can give informed consent, or I have someone who can do it on my behalf.
See 13 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by an infusion of HERV-E TCR transduced CD8+/CD34+ enriched T-cells and IL-2 administration

2-3 weeks
Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinic visits every few weeks for 2 years, and then as determined by their doctor

Up to 15 years
One- or two-day clinic visits every few weeks

Long-term follow-up

Participants will have follow-up checks for up to 15 years to monitor long-term safety and effectiveness

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

  • Cell Infusion
Trial Overview The trial is testing gene transfer therapy where patients' white blood cells are modified in a lab to fight kidney cancer. This involves leukapheresis (blood filtration), chemotherapy drugs, cell modification, reinfusion of changed cells into the patient's body, and follow-up visits for up to 15 years.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Level 4 is 5 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimental Treatment1 Intervention
Group II: Level 3 is 1 x 10^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimental Treatment1 Intervention
Group III: Level 2 is 5 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimental Treatment1 Intervention
Group IV: Level 1 is 1 x 10^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weightExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials
3,987
Recruited
47,860,000+

Loyola University Medical Center (LUMC)

Collaborator

Trials
1
Recruited
20+

Published Research Related to This Trial

Immunotherapy using tumor-infiltrating lymphocytes (TIL) shows promise as a new treatment for kidney cancer metastases, which are difficult to treat with traditional methods like surgery and chemotherapy.
In early clinical trials, activated lymphocytes, cultivated with Interleukin 2 to enhance their cancer-fighting abilities, have demonstrated encouraging results, indicating a potential breakthrough in cancer treatment.
[A new therapeutic concept in the treatment of metastatic cancers of the kidney: the TIL (tumor infiltrating lymphocytes)].Peyret, C.[2006]
Cellular therapy for renal cell carcinoma should be integrated with immunotherapy strategies due to the cancer's known sensitivity to such treatments.
While initial cellular therapies focused on Lymphokine Activated Killer (LAK) cells and Tumor Infiltrating Lymphocytes (TIL), current major evaluations are centered on dendritic cells and allogeneic blood stem cell transplantation.
[Cell therapy in renal cell carcinoma].Ravaud, A.[2009]
The study demonstrated the feasibility and safety of using ex vivo-expanded NK-92 cells as an allogeneic immunotherapy in 12 patients with refractory renal cell cancer and melanoma, with mild and transient toxicities observed during treatment.
One patient with renal cell cancer survived for 4 years post-infusion, indicating potential long-term benefits, while responses varied among other patients, highlighting the need for further research into this NK-cell based therapy.
Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial.Arai, S., Meagher, R., Swearingen, M., et al.[2022]

Citations

Study Details | NCT03354390 | HERV-E TCR Transduced ...This research protocol is therefore designed to evaluate the safety and effectiveness of infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells in HLA-A ...
HERV-E TCR Transduced CD8+/CD34+ T-cells in Treating ...This phase I trial studies the side effects of HERV-E TCR transduced CD8+/CD34+ T-cells in treating patients with clear cell renal cell cancer that has spread ...
Phase I results of human endogenous retrovirus type-E ...Final results of a phase I trial of HERV-E TCR transduced T cells for the treatment of HLA-A*11 patients with metastatic clear cell renal cell carcinoma (mccRCC) ...
4.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39266213/
Regression of renal cell carcinoma by T cell receptor ...This is the first report showing that human ccRCC cells can be selectively recognized and killed by TCR-engineered T cells targeting a HERV-derived antigen.
HERV-E TCR Transduced Autologous T Cells in People ...... infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells. To mediate T cell survival and sustain function, moderate-doses of IL-2 (aldesleukin) will be ...
NCT03354390 | HERV-E TCR Transduced Autologous T Cells in ...Allogeneic hematopoietic stem cell transplantation is also capable of inducing prolonged disease regression in patients with metastatic clear cell RCC (ccRCC).
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