48 Participants Needed

CAR-NK Cell Therapy for Blood Cancers

CH
Overseen ByChitra Hosing
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.

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.

What data supports the effectiveness of the treatment CAR-NK Cell Therapy for Blood Cancers?

Research shows that NK cells (a type of immune cell) engineered to express IL-15 and a chimeric antigen receptor (CAR) can effectively target and kill cancer cells, such as those in leukemia and lymphoma, without causing harmful side effects like graft-versus-host disease. This approach has shown promising results in preclinical models, suggesting it could be a powerful treatment for blood cancers.12345

Is CAR-NK cell therapy generally safe for humans?

CAR-NK cell therapy is considered to have superior safety compared to CAR-T cell therapy, as it does not cause graft-versus-host disease (GVHD), cytokine release syndrome (CRS), or neurotoxicity, which are common side effects of CAR-T cell therapy.36789

How is the CAR-NK cell treatment for blood cancers different from other treatments?

The CAR-NK cell treatment is unique because it uses natural killer (NK) cells from cord blood, which can target cancer cells without causing graft-versus-host disease (a condition where donor cells attack the recipient's body). This treatment is 'off-the-shelf', meaning it can be prepared in advance and used for multiple patients, unlike traditional CAR-T cell therapies that require customization for each individual.3781011

Research Team

ch

chitra hosing

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.
See 15 more

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.
See 14 more

Timeline

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

Treatment Details

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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Phase 2 Dose LevelExperimental Treatment3 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 LevelExperimental Treatment3 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.

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

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.
Exploiting Human NK Cells in Tumor Therapy.Vacca, P., Pietra, G., Tumino, N., et al.[2020]
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.
Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Ma, S., Caligiuri, MA., Yu, J.[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.
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]

References

Exploiting Human NK Cells in Tumor Therapy. [2020]
Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy. [2023]
Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. [2021]
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. [2020]
5.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review. [2023]
CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer. [2023]
The tricks for fighting against cancer using CAR NK cells: A review. [2022]
Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. [2022]
Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
CAR-NK cell therapeutics for hematologic malignancies: hope is on the horizon. [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]
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