80 Participants Needed

NK Cells + Chemotherapy for Blood Cancers

DM
Overseen ByDavid Marin
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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 with leukemia, lymphoma, or multiple myeloma. Immune system cells (such as NK cells) are made by the body to attack foreign or cancerous cells. Researchers think that NK cells you receive from a donor may react against cancer cells in your body, which may help to control the disease.

Will I have to stop taking my current medications?

The trial protocol allows patients to continue certain medications like Hydroxyurea and tyrosine kinase inhibitors until shortly before starting the trial treatment. However, other anti-cancer agents and investigational drugs must be stopped. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment CAR.70/IL15-transduced CB-NK cells for blood cancers?

Research shows that cord blood-derived NK cells engineered to express IL-15 and a chimeric antigen receptor (CAR) can effectively kill cancer cells and prolong survival in animal models, suggesting potential for treating blood cancers. Additionally, a study found that using cord blood-derived NK cells as maintenance therapy after stem cell transplantation improved patient outcomes, indicating their promise in reducing relapse rates and enhancing survival.12345

Is the combination of NK cells and chemotherapy safe for treating blood cancers?

Research shows that NK cells engineered with CAR technology, like CAR.70/IL15-transduced CB-NK cells, have been used safely in humans, with only mild infusion reactions reported in some cases. These cells do not cause graft-versus-host disease (a condition where donor cells attack the recipient's body) and have built-in safety measures to limit toxicity.12567

How is the treatment with CAR.70/IL15-transduced CB-NK cells different from other treatments for blood cancers?

This treatment uses engineered natural killer (NK) cells from cord blood, which are modified to express IL-15 and a chimeric antigen receptor (CAR) targeting CD19, allowing them to effectively attack cancer cells without causing graft-versus-host disease (GVHD), a common issue with other cell therapies. Unlike traditional CAR-T cell therapies, this approach offers an 'off-the-shelf' solution that is easier to produce and administer, potentially improving accessibility and reducing costs.128910

Research Team

David Marin | MD Anderson Cancer Center

David Marin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults aged 18-75 with certain blood cancers (like leukemia, lymphoma) that have a specific marker called CD70. They must be at least 3 weeks out from their last chemotherapy, have good organ function, and not be pregnant or fathering a child. Participants need to use effective birth control during the study and for three months after.

Inclusion Criteria

My blood cancer cells show a high level of CD70.
I can care for myself but may not be able to do active work.
Patients must meet diseases specific eligibility criteria
See 21 more

Exclusion Criteria

I am not on high-dose steroids or certain immune treatments right before joining.
I have not had an active autoimmune disease in the last year.
I am currently on immunosuppressive therapy.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with Cyclophosphamide and Fludarabine phosphate

1-2 weeks

CAR-NK Cell Treatment

Participants receive a single flat dose of CAR.70/IL15-transduced CB-NK cells

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • CAR.70/IL15-transduced CB-NK cells
  • Cyclophosphamide
  • Fludarabine phosphate
Trial OverviewThe trial is testing whether donor-derived natural killer (NK) cells engineered with CAR.70/IL15 can fight cancer when given alongside chemo drugs Cyclophosphamide and Fludarabine phosphate. It's in early stages to check safety and how well it works.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Fludarabine phosphateExperimental Treatment2 Interventions
Fludarabine is dosed using actual body weight.
Group II: CyclophosphamideExperimental Treatment2 Interventions
Cyclophosphamide is dosed per adjusted body weight for patients weighing \> 20% above their ideal body weight using the calculation.
Group III: CAR.70/IL15-transduced CB-NK cellsExperimental Treatment1 Intervention
Patients will receive a single flat dose of CAR-NK.

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Findings from Research

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.
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]
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.
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer.Mehta, RS., Rezvani, K.[2019]
The study successfully developed CAR-NK cells targeting NKG2D ligands using a non-viral piggyBac transposon technology, showing effective cancer cell lysis in vitro and tumor growth inhibition in an in vivo AML model.
Co-expressing interleukin-15 (IL-15) with the NKG2D CAR significantly enhanced the persistence and antileukemic activity of the CAR-NK cells, leading to improved tumor control and extended survival in treated mice.
piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells.Du, Z., Ng, YY., Zha, S., et al.[2021]

References

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. [2021]
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. [2019]
piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells. [2021]
Engineering CAR-NK cells to secrete IL-15 sustains their anti-AML functionality but is associated with systemic toxicities. [2022]
A pilot study of cord blood-derived natural killer cells as maintenance therapy after autologous hematopoietic stem cell transplantation. [2023]
Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. [2022]
The tricks for fighting against cancer using CAR NK cells: A review. [2022]
[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives]. [2021]
NK Cell-Based Immunotherapy for Hematological Malignancies. [2023]
Recent advances in chimeric antigen receptor natural killer cell therapy for overcoming intractable hematological malignancies. [2021]