CAR-NK Cell Therapy for Blood Cancers

Overseen By Chitra Hosing

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Phase 1 and Phase 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new therapy using special cells, called CAR-NK cells, to treat certain blood cancers. The main goal is to determine if this treatment is safe and effective for people with difficult-to-treat cancers like T-cell malignancies, mantle cell lymphoma, and chronic lymphocytic leukemia. Participants will receive varying doses to identify the optimal one. This trial suits individuals who have tried other treatments for these specific blood cancers and still have ongoing disease. 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 novel therapy.

Will I have to stop taking my current medications?

You may need to stop some medications. You must be at least 3 weeks from your last cytotoxic chemotherapy and stop tyrosine kinase inhibitors or other targeted therapies at least three days before starting the trial's chemotherapy. The protocol does not specify other medications, so check with the trial team for guidance.

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

Research shows that a new treatment using special cells, called CAR.5/IL15-transduced CB-NK cells, is being tested for safety in treating blood cancers. Earlier studies found that these cells can effectively target certain blood cancers, but more testing is needed to ensure their safety for humans.

This trial is in its early stages (Phase 1/2), focusing mainly on checking safety and finding the right dose. Researchers are learning how well patients handle the treatment and what side effects might occur.

Early trials like this are designed to closely monitor participants for any negative effects. Although detailed information may be limited, the early trial phase prioritizes safety. Participants are usually monitored carefully to ensure their well-being throughout the study. ^{1 2 3 4 5}

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

CAR-NK Cell Therapy for blood cancers is unique because it uses genetically engineered natural killer (NK) cells derived from umbilical cord blood. Unlike conventional treatments like chemotherapy or stem cell transplants, this therapy specifically targets cancer cells with a chimeric antigen receptor (CAR) that enhances the NK cells' ability to identify and destroy cancer more effectively. Additionally, the inclusion of interleukin-15 (IL-15) helps in sustaining and expanding these NK cells in the patient's body, which could lead to more durable responses and fewer side effects. Researchers are excited because this approach offers a promising new avenue for tackling difficult-to-treat blood cancers with potentially better outcomes and improved safety profiles.

What evidence suggests that CAR.5/IL15-transduced CB-NK cells could be an effective treatment for blood cancers?

Research has shown that a new treatment using specially modified immune cells, called CAR.5/IL15-transduced CB-NK cells, may help treat blood cancers like T-cell malignancies. These cells target a specific marker, CD5, found on T-cells, and have demonstrated high effectiveness in early tests. They also contain IL-15, a protein that enhances their strength and lifespan. In this trial, participants will receive CAR.5/IL15-transduced CB-NK cells at different dose levels to determine the optimal dose. Although more research is needed, initial results are promising, indicating that these cells can successfully attack and destroy cancerous T-cells. The treatment remains under study, but the findings so far offer hope for patients with these challenging cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

chitra hosing

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with relapsed/refractory blood cancers like T-cell malignancies, mantle cell lymphoma, and chronic lymphocytic leukemia. They must have tried at least two treatments before, be in good physical condition (Karnofsky score >50%), not pregnant or breastfeeding, and willing to use birth control. Patients should not have severe ongoing side effects from past treatments or active infections.

Inclusion Criteria

My heart functions well, with no serious fluid around it or uncontrolled heart rhythm problems.

My kidney function is normal, with creatinine ≤ 1.5 or eGFR ≥ 60.

My blood cancer cells show high levels of CD5.

Exclusion Criteria

I am not on high-dose steroids or recent strong immune treatments.

I have active hepatitis B or C.

You have another serious medical condition that could put your health at risk, as determined by the doctor in charge of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

All patients receive lymphodepleting chemotherapy with Cyclophosphamide and Fludarabine

1-2 weeks

Treatment

Participants receive CAR.5/IL15-transduced CB-NK cells at various dose levels

Phase 1 and Phase 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

through study completion, an average of 1 year

What Are the Treatments Tested in This Trial?

Interventions

• CAR.5/IL15-transduced CB-NK cells
• Cyclophosphamide
• Fludarabine Phosphate

Trial Overview The study tests CAR 5/IL15-transduced CB-NK cells combined with Fludarabine Phosphate and Cyclophosphamide chemotherapy to find the safest and most effective dose for treating certain blood cancers that haven't responded well to other therapies.

How Is the Trial Designed?

Group I: Phase 2 Dose Level Experimental Treatment 3 Interventions

Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.

Group II: Phase 1 Dose Level Experimental Treatment 3 Interventions

CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.

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

Interleukin-15 (IL-15) is essential for regulating the immune functions of natural killer (NK) cells, which are important for fighting tumors, making it a key target in cancer therapies.

Current clinical trials are exploring the use of IL-15 and its analogs, as well as genetically modifying NK cells to enhance their effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy. Ma, S., Caligiuri, MA., Yu, J.[2023]

CAR T-cell therapy targets specific cancer cells while minimizing damage to normal cells, showing promising results in treating acute myeloid leukemia and various solid tumors like pancreatic and ovarian cancers.

Despite its effectiveness, CAR T-cell therapy can cause adverse effects such as cytokine release syndrome and off-target toxicity, highlighting the need for ongoing improvements in safety and efficacy through innovations like SUPRA CAR technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review. Sharma, R., Suravarjhula, L., Banerjee, M., et al.[2023]

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 T cell therapy is a promising treatment for Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL), but it carries risks such as cytokine release syndrome and neurotoxicity.

Natural Killer (NK) cells from adult peripheral blood and umbilical cord blood show potential as safer alternatives for CAR therapy, with adult NK cells being slightly more effective at targeting cancer cells, while cord blood NK cells are easier to stimulate and more consistent across donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells. Herrera, L., Santos, S., Vesga, MA., et al.[2021]

CAR-T-cell therapy is effective for treating blood cancers but is associated with significant treatment-related toxicity and side effects.

CAR-modified natural killer (CAR-NK) cells may offer a safer and more effective alternative for immunotherapy in hematologic malignancies due to their MHC-independent recognition and strong antitumor functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-NK cell therapeutics for hematologic malignancies: hope is on the horizon. Xu, KL., Cheng, H.[2022]

Ectopic expression of IL-15 in human NK cells enhances their growth and cytotoxicity without the need for IL-2, allowing for effective proliferation and activation of these cells.

NK cells modified to express both IL-15 and a chimeric antigen receptor (CAR) targeting cancer cells showed improved selective killing of resistant breast carcinoma cells, indicating a promising strategy for enhancing the efficacy of NK cell-based cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. Sahm, C., Schönfeld, K., Wels, WS.[2020]

CAR-modified T cell therapy has shown great success in treating blood cancers but is associated with significant risks like graft-versus-host disease (GVHD) and cytokine release syndromes (CRS).

CAR-NK cell therapy presents a safer alternative, as it avoids these adverse effects and offers better anti-tumor activity without the need for HLA matching, making it a promising 'off-the-shelf' treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer. Włodarczyk, M., Pyrzynska, B.[2023]

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]

CAR-NK cells, which are genetically engineered natural killer cells, show promise as a safer alternative to CAR-T cell therapy, potentially reducing the risk of severe side effects like cytokine release syndrome and tumor lysis syndrome.

Studies have successfully transduced both human primary NK cells and the NK-92 cell line to express CARs targeting various cancers, indicating their effectiveness in both pre-clinical and clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tricks for fighting against cancer using CAR NK cells: A review. Vahidian, F., Khosroshahi, LM., Akbarzadeh, M., et al.[2022]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05110742

NCT05110742 | Phase I/II Study of CD5 CAR Engineered ... To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, ...

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0526.html

Phase I/II Study of CD5 CAR Engineered IL15-Transduced ... To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11980226/

Engineering CD5-targeting CAR-NK cells from peripheral ... This study developed a controllable CD5 CAR-NK cells that exhibit high efficacy against T-cell malignancies, although further validation is necessary to assess ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6063081/

Cord blood NK cells engineered to express IL-15 and a ... The median CAR-NK transduction efficiency on day 14 of culture was 66.6% (range, 47.8–87.4%; n=18) (Supplementary Fig. 1A). Table 1 summarizes data on fold- ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07137481

NCT07137481 | Phase II Study of CD5 CAR Engineered ... To determine the safety and efficacy (1-year PFS) of iC9/CD5CAR/IL-15 NK cells as consolidation in patients with aggressive T-cell malignances ...

6. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

7. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00633-8

The clinical landscape of CAR NK cells Here we explore the current clinical landscape of CAR NK cells, and their application in hematologic malignancies and solid cancers.