NK Cell Therapy + Chemotherapy for Advanced Kidney, Lung, or Bone Cancer

Overseen By David Hong, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer agents, Immunosuppressives

Disqualifiers: Infections, Autoimmune disease, Neurological disorders, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment that combines NK cell therapy with chemotherapy for individuals with advanced kidney, lung, or bone cancer. The goal is to determine the safe dose of donated NK cells (a type of immune cell) that can be administered alongside chemotherapy. Patients with advanced renal cell carcinoma, mesothelioma, or osteosarcoma, who have not responded to previous treatments, might be suitable candidates for this trial. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as cytotoxic chemotherapy, tyrosine kinase inhibitors, or other targeted therapies, at least 2 weeks before starting the trial's lymphodepleting chemotherapy. If you are on systemic steroid therapy, you may need to stop or adjust your dose, unless it's a low dose or specific type like topical or inhaled steroids.

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

Research shows that a new treatment using special immune cells, called CAR.70/IL15-transduced CB-derived NK cells, may help fight certain cancers when combined with chemotherapy. Earlier studies examined the safety and tolerability of these immune cells. They target and attack cancer cells through a protein called CD70.

In these studies, patients generally tolerated the treatment well at different doses. However, like any treatment, side effects can occur. Some patients experienced mild to moderate side effects, but serious issues were rare. This suggests the treatment is usually well-tolerated, though further research is needed to confirm this.

Overall, early results indicate the treatment can be safe for people, but ongoing trials aim to find the best dose to use with chemotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the combination of CAR.70/IL15-transduced CB-derived NK cells with chemotherapy for treating advanced kidney, lung, or bone cancer because it offers a novel approach that differs from traditional treatments like targeted therapies and checkpoint inhibitors. Unlike standard treatments, this therapy uses genetically modified natural killer (NK) cells to specifically target and destroy cancer cells, potentially enhancing the body's immune response against the tumors. Additionally, the incorporation of IL-15 aims to boost the survival and activity of these NK cells, potentially leading to more effective and sustained cancer control. This innovative mechanism could offer new hope for patients who have not responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced kidney, lung, or bone cancer?

In this trial, participants will receive a combination of CAR.70/IL15-transduced NK cells and chemotherapy. Research shows that CAR.70/IL15-transduced NK cells target CD70, a protein found on some cancer cells. These specially engineered NK cells, derived from cord blood, produce interleukin-15 (IL-15), which aids the immune system in fighting cancer. Early studies suggest these cells can effectively attack cancer cells in kidney cancer, mesothelioma, and bone cancer. This therapy combines NK cells with chemotherapy to enhance the body's cancer-fighting ability. Although research in humans continues, this approach appears promising based on the function of these NK cells in the body. ^{1 2 3 4 6}

Who Is on the Research Team?

David Hong, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-80 with advanced renal cell carcinoma, mesothelioma, or osteosarcoma showing CD70 expression can join. They must have proper organ function and agree to birth control use. Exclusions include serious medical conditions, recent heart issues or major surgery, other cancer treatments or investigational drugs within specific time frames.

Inclusion Criteria

I've had targeted radiation before chemo, but still have untreated cancer areas.

I can do all my daily activities without help.

My cancer shows high CD70 levels in tests.

Exclusion Criteria

I do not have any serious health conditions that could make the treatment unsafe for me.

I have active hepatitis B or C, or HIV with a detectable viral load.

I have symptoms or uncontrolled issues in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to NK cell infusion

1-2 weeks

NK Cell Infusion

Participants receive CAR.70/IL15-transduced cord blood-derived NK cells at assigned dose levels

1 week

Follow-up

Participants are monitored for safety, tolerability, and antitumor activity after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CAR.70/IL15-transduced CB-derived NK cells
• Cyclophosphamide
• Fludarabine phosphate

Trial Overview The trial is testing the safety and dosage of CAR.70/IL15-transduced CB-derived NK cells combined with lymphodepleting chemotherapy (Fludarabine phosphate and Cyclophosphamide) in patients with certain advanced cancers to see how well they work together.

How Is the Trial Designed?

Group I: Chemotherapy and NK Cell Infusion Experimental Treatment 3 Interventions

Participants will be assigned to a dose level of NK cells. A computer will decide by chance which of the dose level you will receive, and this will not be based on the doctor's or patient's decision. Up to 5 dose levels of NK cells will be tested. Each new patient will receive a different dose. If any dose shows to be not tolerable, this dose and the higher doses will not be given anymore.

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

Genetic engineering of natural killer (NK) cells can enhance their tumor-killing ability and specificity, addressing limitations in their effectiveness in cancer immunotherapy.

Chimeric antigen receptor (CAR) NK cells, particularly those derived from human pluripotent stem cells, show promise in targeting both blood and solid tumors, providing a stable and expandable source for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prospect of genetically engineering natural killer cells for cancer immunotherapy. Poon, AYC., Sugimura, R.[2022]

Engineered cord blood-derived natural killer (NK) cells, modified with CAR-CD19 and IL-15, showed effective targeting and killing of leukemia cells in laboratory tests and improved survival in a mouse model of lymphoma.

This approach not only enhances the efficacy of NK cells in treating cancers but also includes a safety mechanism (the iC9 suicide gene) to eliminate the cells if necessary, reducing the risk of adverse effects like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Liu, E., Tong, Y., Dotti, G., et al.[2021]

CAR-modified Natural Killer (NK) cells present a promising alternative to CAR T cells for cancer treatment due to their MHC-independency, shorter lifespan, and potential for off-the-shelf use, making them a flexible option for targeting tumors.

The review highlights ongoing challenges in enhancing the efficacy and safety of CAR NK cells, particularly in solid tumors, and discusses strategies to improve their persistence and function in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. Elahi, R., Heidary, AH., Hadiloo, K., et al.[2022]

Adoptive cell therapy, particularly using CAR T cells, has shown great promise in treating advanced cancers, but the need for patient-specific products limits its widespread use.

Natural killer (NK) cells offer a safer alternative as an allogeneic 'off-the-shelf' therapy, as they do not cause graft-versus-host disease (GVHD) and can be engineered with CARs to enhance their anti-tumor effects, making them a focus for future cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. Mehta, RS., Rezvani, K.[2019]

Natural Killer (NK) cells are crucial in fighting tumors and can be enhanced through immunotherapy, but traditional methods like IL-2 infusion can cause significant toxicity, limiting their use.

Innovative approaches like CAR-engineered NK cells offer a promising 'off-the-shelf' therapy option that avoids complications like graft-versus-host disease (GvHD) and can be sourced from unrelated donors, potentially improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting Human NK Cells in Tumor Therapy. Vacca, P., Pietra, G., Tumino, N., et al.[2020]

Genetically-engineered universal antigen presenting cells (uAPC) can significantly enhance the growth of both non-transduced and CAR-transduced natural killer (NK) cells, achieving over 900-fold expansion in just 2 weeks with high purity (over 99.9%).

NK cells expanded using uAPCs exhibit improved metabolic fitness and greater effectiveness against tumor cells, making them a promising option for adoptive CAR NK cell-based cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells. Liu, E., Ang, SOT., Kerbauy, L., et al.[2022]

CAR-engineered natural killer (CAR-NK) cells show remarkable efficacy in cancer therapy and may offer advantages over traditional CAR-T cell therapies, particularly due to their ability to be used as 'off-the-shelf' products.

The review highlights the mechanisms of CAR-NK cells' anti-tumor activity and discusses ongoing challenges and clinical trials, suggesting that CAR-NK therapy holds significant promise for future cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential. Wang, X., Yang, X., Yuan, X., et al.[2022]

CAR-T cell therapy has transformed treatment for relapsed or refractory B-cell cancers, but it faces challenges such as variable T cell quality, high costs, and potential toxicities.

Natural Killer (NK) cells present a promising alternative for cancer treatment, as they can be used in allogeneic settings with fewer side effects, and recent advancements in CAR-NK cell engineering enhance their effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives]. Nguyen, S., Lacan, C., Roos-Weil, D.[2021]

Two methods for producing interleukin-15-activated NK cells were developed, yielding similar quantities of NK cells but with significantly lower T cell contamination in the NKIL15 product, enhancing its potential for clinical use.

Both NKIL15 and NKAE cell products demonstrated increased cytotoxic activity against cancer cells without harming healthy cells, and showed no genetic alterations, indicating their safety for therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do we manufacture clinical-grade interleukin-15-stimulated natural killer cell products for cancer treatment? Fernández, L., Leivas, A., Valentín, J., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05703854

NCT05703854 | Study of CAR.70-engineered IL15 ... Primary Objective: To determine the safety, tolerability, and optimal cell dose of chimeric antigen receptor (CAR).70/interleukin (IL)15-transduced cord ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05703854?cond=NCT05703854&rank=1

Study of CAR.70-engineered IL15-transduced Cord Blood- ... Primary Objective: To determine the safety, tolerability, and optimal cell dose of chimeric antigen receptor (CAR).70/interleukin (IL)15-transduced cord ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1936523325002864

CD70-targeted CAR-T/NK therapy: Rationale, advances, ... IL-15 NK cells are cord blood-derived, IL-15-producing CAR-NK cells designed to target CD70. The CAR construct consists of an anti-CD70 single-chain variable ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/C183511?pn=1

Clinical Trials Using Allogeneic Anti-CD70-CAR-IL-15 ... CD70 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells and Lymphodepleting Chemotherapy for the Treatment of Advanced Renal Cell Carcinoma ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12367655/

Recent advances in tumor immunotherapy based on NK cells Study of CAR.70-engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction with Lymphodepleting Chemotherapy for the Management of Advanced Renal ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0386.html

engineered IL15-transduced cord blood-derived NK cells ... The goal of this clinical research study is to learn about the safety of giving immune cells called natural killer (NK) cells with chemotherapy to patients ...