124 Participants Needed

CD70-Targeted CAR T-cell Therapy for Cancer

NS
Overseen ByNCI SB Immunotherapy Recruitment Center
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must have completed any prior systemic therapy before enrolling, and you cannot be on systemic steroid therapy or other investigational agents.

What data supports the effectiveness of the CD70-targeted CAR T-cell treatment for cancer?

Research shows that CD70-targeted CAR T-cells can effectively recognize and kill cancer cells that express CD70, leading to tumor regression in animal models. This suggests that the treatment could be promising for cancers with CD70 expression.12345

Is CD70-targeted CAR T-cell therapy generally safe for humans?

CAR T-cell therapies, including those targeting CD70, can cause serious side effects like prolonged blood-related issues and damage to healthy tissues that share the target with cancer cells. These treatments may also lead to life-threatening reactions due to their strong immune response.678910

What makes the CD70-targeted CAR T-cell treatment unique for cancer?

This treatment is unique because it uses genetically modified T cells to specifically target CD70, a protein found on certain cancer cells but not widely present on normal cells, potentially reducing side effects compared to other therapies that target more common proteins.124611

What is the purpose of this trial?

Background:In a new cancer therapy, researchers take a person s blood, select a certain white blood cell to grow in the lab, and then change the genes of these cells using a virus. The cells are then given back to the person. This is called gene transfer. For this study, researchers will modify the person s white blood cells with anti-CD70.Objectives:To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe.Eligibility:Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer.Design:Participants will be screened with medical history, physical exam, scans, and other tests. They may by admitted to the hospital. Leukapheresis will be performed. For this, blood is removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.Eligible participants will have an intravenous catheter placed in their upper chest. Over several days, they will get chemotherapy drugs and the anti-CD70 cells. They will recover in the hospital.Participants will take an antibiotic for 6 months after treatment. They will repeat leukapheresis.Participants will visit the clinic every 1-3 months for the first year after treatment, every 6 months for the second year, and then as determined by their physician. Follow-up visits will take 1-2 days. At each visit, participants will have lab tests, imaging studies, and a physical exam.Throughout the study, blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact.

Research Team

JC

James C Yang, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18-72 with CD70-expressing cancers like kidney, breast, or ovarian cancer who've tried at least one standard treatment without success. They must have a certain level of blood cells and organ function, not be pregnant or breastfeeding, HIV negative, and willing to use birth control.

Inclusion Criteria

I have up to 3 small, symptom-free brain tumors or have had brain surgery.
I am fully active or restricted in physically strenuous activity but can do light work.
You do not have hepatitis B or C. If you test positive for hepatitis C, you need to have another test to make sure the virus is not in your blood.
See 18 more

Exclusion Criteria

I am currently on systemic steroid therapy.
I have an autoimmune disease that needs treatment to suppress my immune system.
You've had a serious allergic reaction to cyclophosphamide, fludarabine, or aldesleukin in the past.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine, followed by anti-hCD70 CAR transduced PBL and high-dose aldesleukin

6 weeks
Hospital stay for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations approximately 6 weeks after treatment and regular follow-up visits

12 weeks
Clinic visits every 1-3 months for the first year, then every 6 months for the second year

Long-term follow-up

Participants continue to be monitored for long-term safety and effectiveness, with visits as determined by their physician

Up to 2 years

Treatment Details

Interventions

  • Anti-hCD70 CAR transduced PBL
Trial Overview The trial tests gene transfer therapy using modified white blood cells targeting CD70 on cancer cells. It includes chemotherapy drugs (cyclophosphamide and fludarabine) and aldesleukin before infusing the engineered cells. Participants will be monitored regularly for tumor response and safety.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: 2/Phase IIExperimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin
Group II: 1/Phase IExperimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Genetically modified T cells targeting CD70 show promise for treating a wide range of hematologic malignancies and some solid tumors, expanding the potential of T-cell therapies beyond B cell-derived cancers.
The study demonstrated that CD70-specific T cells can effectively recognize and kill tumor cells, leading to sustained regression of tumors in mouse models, indicating their potential as a new immunotherapy option.
T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies.Shaffer, DR., Savoldo, B., Yi, Z., et al.[2021]
CAR-T cell therapy is emerging as a promising immunotherapy for hematological cancers, particularly by targeting immune checkpoint proteins on tumor cells.
The review discusses various CAR-T cells targeting proteins like CD70, CD47, and PDL-1, which can effectively reduce tumor cells by overcoming inhibitory signaling pathways, suggesting a potential for improved cancer treatment strategies.
CAR-T Cells Targeting Immune Checkpoint Pathway Players.Golubovskaya, V.[2022]
Chimeric PD1 (chPD1) T-cells effectively target and kill a variety of solid tumors, including melanoma, pancreatic, and breast cancer, by recognizing PD1 ligands present on their surface, demonstrating their potential as a novel cancer therapy.
Although chPD1 T-cells did not survive beyond 14 days in the body, they successfully induced long-term anti-tumor memory responses, suggesting that they could provide lasting protection against cancer recurrence.
T-cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumour burden in multiple murine syngeneic models of solid cancer.Parriott, G., Deal, K., Crean, S., et al.[2021]

References

T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. [2021]
CAR-T Cells Targeting Immune Checkpoint Pathway Players. [2022]
T-cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumour burden in multiple murine syngeneic models of solid cancer. [2021]
Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers. [2019]
Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. [2023]
A rational mouse model to detect on-target, off-tumor CAR T cell toxicity. [2021]
Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? [2017]
Prolonged hematologic toxicity following treatment with chimeric antigen receptor T cells in patients with hematologic malignancies. [2021]
Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Challenges to chimeric antigen receptor (CAR)-T cell therapy for cancer. [2014]
Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies. [2023]
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