Personalized NK Cell Therapy for Blood Cancer

Overseen By Amanda Olson, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV positive, Uncontrolled serious medical condition, Active CNS disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a personalized therapy using natural killer (NK) cells to treat certain blood cancers, such as leukemia, lymphoma, and multiple myeloma. Researchers aim to determine if this approach, administered after chemotherapy and a cord blood transplant, can more effectively target and eliminate residual cancer cells while reducing complications. The trial includes different treatment arms based on specific cancer types and patient conditions. Individuals with these blood cancers who have already tried standard treatments but still need more options might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that NK-92 cell therapy, a type of natural killer cell treatment, has been tested in several studies. These studies found no major side effects, and in some cases, patients even improved. Reports indicate that patients tolerated the treatment well. The most common side effect was fatigue, characterized by tiredness or low energy. This suggests that the treatment is generally safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they use personalized natural killer (NK) cell therapy to target blood cancers in a way that current treatments like chemotherapy and radiation might not. Unlike typical treatments, these therapies involve infusing patients with NK-92 cells, which are a type of immune cell that can specifically identify and attack cancer cells. Each treatment regimen is combined with an umbilical cord blood transplant, which provides a new source of healthy blood cells. This approach not only aims to improve cancer targeting but also potentially leads to fewer side effects and a more personalized treatment experience.

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

Research has shown that NK-92 cells, a type of natural killer cell, could help treat various cancers. In this trial, participants will receive NK-92 cell infusions as part of different treatment regimens. Studies have found that these infusions can lead to cancer improvement, with 37.5% of patients experiencing complete or partial remission. Designed to destroy leftover cancer cells after treatments like chemotherapy, these cells have proven safe in several clinical trials, showing only minor side effects. This makes them a promising option for treating blood cancers such as leukemia, lymphoma, and multiple myeloma. ^{1 2 3 6 7}

Who Is on the Research Team?

Amanda Olson

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 15-80 with various blood cancers or myelodysplastic syndromes who have not responded well to standard treatments. They must be physically able to tolerate the transplant, with specific heart, kidney, and liver function requirements. Women of childbearing age must test negative for pregnancy. Those with curative treatment options elsewhere or certain serious health conditions are excluded.

Inclusion Criteria

I do not have any curative treatment options available.

Patients enrolled in this study may be enrolled on other supportive care investigational new drug (IND) studies at the discretion of the principal investigator (PI)

My CML is in the second chronic or accelerated phase.

Exclusion Criteria

I do not have any severe health issues that my current treatments can't control.

I have a matching stem cell donor available.

You have HIV, which will be checked with a special test for the virus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Patients receive a preparative regimen including chemotherapy and total body irradiation before transplantation

9 days

Umbilical Cord Blood Transplant

Patients undergo umbilical cord blood transplantation

1 day

NK Cells Infusion

Patients receive NK cells infusion to enhance immune response and reduce graft versus host disease

150 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Visits at 1, 7, 14, 28, 45, 60, and 100 days, and at 6, 9, and 12 months, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Natural Killer Cell Line NK-92

Trial Overview The study tests personalized NK cell therapy following chemotherapy and umbilical cord blood transplantation in patients with leukemia, lymphoma, multiple myeloma, or myelodysplastic syndrome. It aims to see if NK cells can kill remaining tumor cells and reduce graft versus host disease after transplant.

How Is the Trial Designed?

Group I: Reduced intensity regimen 3 Experimental Treatment 6 Interventions

Patients receive anti-thymocyte globulin IV over 4 hours on days -7 and -6, fludarabine phosphate IV over 1 hour on days -5 to -2, and melphalan IV over 30 minutes on day -2. UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0. NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Group II: Non-myeloablative regimen 2 Experimental Treatment 8 Interventions

Patients with CD20 positive malignancies receive rituximab IV over 6 hours on day -9. Patients receive anti-thymocyte globulin IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 1 hour on days -6 to -3, and cyclophosphamide IV over 3 hours on day -6 and undergo TBI on day -1 at the discretion of the investigator(s). UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0. NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Group III: Myeloablative regimen 1 Experimental Treatment 8 Interventions

Patients receive anti-thymocyte globulin IV over 4 hours on days -9 and -8, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -7 to -4. Patients undergo TBI on day -3. UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0. NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Natural killer (NK) cells offer a promising alternative to T lymphocyte-based immunotherapy for treating hematological malignancies due to their strong ability to target and destroy tumor and virus-infected cells without the risk of graft-versus-host disease.

Advancements in NK cell manufacturing allow for the production of large quantities of these cells without the need for genetic modifications, potentially enhancing their clinical efficacy and making them more accessible for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural killer cells: Innate immune system as a part of adaptive immunotherapy in hematological malignancies. Demel, I., Koristek, Z., Motais, B., et al.[2022]

NK-92 cells are the only NK cell line that has been successfully infused into patients with advanced cancer, showing clinical benefits and minimal side effects, making them a promising option for cancer therapy.

Unlike other NK cell lines, NK-92 can be easily genetically modified to enhance its ability to target specific tumor antigens, which may improve its effectiveness in treating cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural Killer Cells for Immunotherapy - Advantages of the NK-92 Cell Line over Blood NK Cells. Klingemann, H., Boissel, L., Toneguzzo, F.[2022]

The study found that a fourth-generation CAR-NK-92 cell, which co-expresses IL-15 and its receptor IL-15/IL-15Rα, significantly improved NK-92 cell proliferation and cytotoxic activity against B-cell leukemia in both laboratory tests and a mouse model.

This enhanced CAR-NK-92 cell approach may help overcome current limitations in NK-92 cell therapies, potentially leading to more effective treatments for B-cell cancers with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect in vivo. Silvestre, RN., Eitler, J., de Azevedo, JTC., et al.[2023]

Natural killer (NK) cells are emerging as powerful agents against leukemia, particularly in the context of allogeneic stem-cell transplantation, where donor NK cells can enhance treatment outcomes.

To effectively utilize NK cells in therapy, researchers are focusing on developing safe and effective methods for generating large quantities of NK cells that maintain their anti-leukemia activity across different patients, while also addressing the need for optimized clinical protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the outcome of leukemia by natural killer cell-based immunotherapeutic strategies. Chouaib, S., Pittari, G., Nanbakhsh, A., et al.[2021]

Natural killer (NK) cells play a crucial role in fighting cancer, but tumors can develop ways to evade or weaken these immune cells, which poses a challenge for effective treatment.

Current strategies in NK cell-based cancer immunotherapy include using stable allogeneic NK cell lines and genetically modifying them to enhance their effectiveness, with several therapeutic NK cell lines currently being tested in preclinical and clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural killer cell lines in tumor immunotherapy. Cheng, M., Zhang, J., Jiang, W., et al.[2022]

Infusions of NK-92 cells, a type of natural killer cell, were well tolerated in 15 patients with advanced, treatment-resistant cancers, with no infusion-related or long-term side effects observed, even at the maximum dose of 10(10) cells/m².

Approximately 75% of patients with lung cancer showed some anti-tumor response, indicating potential efficacy of NK-92 cell therapy in this group, while the development of human leukocyte antigen antibodies was rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with advanced cancer with the natural killer cell line NK-92. Tonn, T., Schwabe, D., Klingemann, HG., et al.[2022]

Activated natural killer (A-NK) cells have not shown clear clinical benefits in cancer therapy, but the NK-92 cell line has demonstrated significant antitumor activity in laboratory studies and in animal models, making it a promising candidate for adoptive immunotherapy.

NK-92 cells, which lack certain receptors but retain strong cytotoxic capabilities, are currently the only NK cell line undergoing clinical trials, with early experiences in patients indicating potential for improved outcomes in advanced cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. Tonn, T., Becker, S., Esser, R., et al.[2022]

Adoptive cell therapy using natural killer (NK) cells shows promise in cancer treatment, particularly for solid tumors, as they can effectively clear tumors without needing prior antigen presentation, unlike T or B cells.

The review discusses various sources for NK cells, including peripheral blood, umbilical cord blood, and induced pluripotent stem cells (iPSCs), highlighting the potential of engineered iPSC-derived NK cells for enhanced and sustained antitumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells. Maddineni, S., Silberstein, JL., Sunwoo, JB.[2022]

NK-92 cells, modified to express high-affinity CD16 receptors and chimeric antigen receptors (CARs), show strong potential as an off-the-shelf cell therapy for cancer treatment due to their ability to recognize and kill tumor cells without the need for HLA matching.

Preliminary phase 1 clinical data suggest that CAR-engineered NK-92 cells can be safely administered to patients, indicating promising safety and efficacy for this innovative immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy. Fabian, KP., Hodge, JW.[2021]

CAR-engineered NK-92 cells have shown promising antitumor activity in preclinical models, demonstrating the ability to target specific cancer antigens and potentially overcome tumor resistance, which is crucial for effective cancer immunotherapy.

The safety of irradiated NK-92 cell infusions has been established in phase I clinical trials, with some patients showing clinical responses, paving the way for further development of these cells as off-the-shelf treatments for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity. Zhang, C., Oberoi, P., Oelsner, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12191011/

The Natural Killer Cell Line NK-92 and Its Genetic Variants The unmodified NK-92 cells have completed several clinical trials confirming no significant side effects and clinical responses. Its CAR ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1465324922010751

The NK-92 cell line—30 years later: its impact on natural ... Infusions of either unmodified or modified NK-92 cells have been reported to be safe and efficacious, leading in some cases to disease remission even in ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14837-y

A systematic review of the last two decades of NK cell-based ... Aligned with our findings, the study reported a 37.5% complete or partial remission rate after NK cell infusion in patients in relapse or ...

4. nature.com nature.com/articles/s41423-024-01145-x

Development of NK cell-based cancer immunotherapies ... Early clinical trials have shown promising outcomes, alongside satisfactory product efficacy and safety. Recent developments have greatly ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00091/full

Advantages of the NK-92 Cell Line over Blood NK Cells NK-92 is also the only cell line product that has been infused into patients with advanced cancer with clinical benefit and minimal side effects. The remarkable ...

6. cell.com cell.com/cancer-cell/abstract/S1535-6108(25)00405-2

Engineered natural killer cells for cancer therapy Early-phase clinical trials have demonstrated remarkable safety and encouraging therapeutic efficacy of chimeric antigen receptor (CAR)-NK cells ...

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1454427/full

Efficacy and safety of natural killer cell therapy in patients ... Safety profiles were favorable, with fatigue being the most common adverse event. Discussion: NK cell therapies represent a promising treatment option for solid ...