CAR NK Cell Therapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome

Not currently recruiting at 7 trial locations

Overseen By Nishi Kothari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nkarta Inc.

Must be taking: Fludarabine, Cyclophosphamide

Must not be taking: Anti-AML/MDS drugs

Disqualifiers: Leukemic meningitis, CNS disease, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NKX101, which uses special immune cells to target and fight blood cancers like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The main goal is to determine the treatment's safety and patient tolerance. The trial involves patients with relapsed or hard-to-treat AML or MDS, specifically those who have not responded to other treatments. Participants should have manageable symptoms, such as the ability to handle daily activities, and need to have certain blood levels checked by their doctor. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain anti-AML/MDS drugs cannot be used within a specific time before starting the trial. It's best to discuss your current medications with the study team to understand any specific requirements.

Is there any evidence suggesting that NKX101 is likely to be safe for humans?

Research has shown that NKX101, a new treatment being tested for certain blood cancers, is generally safe for patients. In early studies, including one involving patients with acute myeloid leukemia (AML), researchers found no serious safety issues. NKX101, made from donor immune cells, targets specific cancer cells. While these early results are encouraging, it is important to remember that this treatment remains in the early testing stages, and further research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NKX101 because it represents a novel approach to treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) by using CAR NK cell therapy. Unlike traditional treatments like chemotherapy, which broadly target rapidly dividing cells, NKX101 uses genetically modified natural killer (NK) cells to specifically recognize and attack cancer cells. This targeted mechanism may lead to more precise and potentially less toxic treatment. Additionally, NKX101 is derived from off-the-shelf donor cells, which could make it more readily available and easier to administer compared to patient-specific therapies.

What evidence suggests that NKX101 might be an effective treatment for AML or MDS?

Research has shown that NKX101, a type of cell therapy under study in this trial, holds potential for treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In some studies, patients with AML that returned or did not respond to other treatments experienced complete remission rates of 20% to 50% after receiving similar therapies. Early results from this trial suggest that NKX101 is safe and well-tolerated by patients. Additionally, the treatment has shown signs of reducing minimal residual disease (MRD), the amount of cancer remaining after treatment. While more research is needed, these early findings are promising for those considering NKX101 in this trial. ^{2 4 5 6 7}

Who Is on the Research Team?

David Shook, MD

Principal Investigator

Nkarta, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndromes (MDS). Participants must have had 1-2 prior treatments, a white blood cell count ≤25 × 10^9/L, and platelets ≥30,000/uL. They need functioning organs and an ECOG status ≤2. A suitable donor for leukapheresis is required if haplo-matched. Birth control use is mandatory.

Inclusion Criteria

White blood cell count of ≤25 × 10^9/L

I've had 1 or 2 treatments for myelodysplastic syndrome.

Platelet count ≥30,000/uL (platelet transfusions acceptable)

Exclusion Criteria

Other: Pregnant or lactating female

My leukemia is specifically acute promyelocytic with a certain genetic feature.

I have leukemia that has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part 1: Dose Finding

Participants receive lymphodepletion followed by weekly doses of NKX101 to determine the optimal dose

3-4 weeks

3-4 visits (in-person)

Treatment - Part 2: Dose Expansion

Participants receive lymphodepletion followed by weekly doses of NKX101 to evaluate safety and efficacy

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety, NKX101 persistence, and response rates

Up to 2 years

Regular visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• NKX101

Trial Overview NKX101 - CAR NK cell therapy is being tested in this Phase 1 study to see how safe and tolerable it is for patients with AML or MDS that has come back or didn't respond to treatment. It's given intravenously and targets NKG2D ligands on cancer cells.

How Is the Trial Designed?

Group I: NKX101 - CAR NK cell therapy Experimental Treatment 1 Intervention

All subjects in Part 1 will receive lymphodepletion with fludarabine/cyclophosphamide followed by 3 or 2 (Regimen A or B, respectively) weekly doses of NKX101. Subjects in Part 2 will receive lymphodepletion with either fludarabine/cyclophosphamide or fludarabine/cytarabine (ara-C), or if the optional arm is opened, lymphodepletion with fludarabine/cyclophosphamide and decitabine, followed by 3 weekly doses of NKX101. Part 2: unrelated off-the-shelf donor derived NKX101 will be used.

Who Is Running the Clinical Trial?

Nkarta Inc.

Lead Sponsor

Trials

2

Recruited

210+

Nkarta, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Published Research Related to This Trial

The study involved 7 pediatric patients with acute myeloid leukemia (AML) who received activated and expanded natural killer (NK) cells as a treatment after chemotherapy, showing that this approach is safe and feasible.

After a median follow-up of 33 months, 85.7% of patients remained in complete remission, and the 3-year overall survival rate was 83.3%, although the small sample size limits definitive conclusions about efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL-Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia. Gómez García, LM., Escudero, A., Mestre, C., et al.[2022]

In a phase 1 trial involving 9 pediatric and young adult patients with relapsed acute myeloid leukemia (AML) after hematopoietic cell transplantation, donor-derived memory-like natural killer (ML NK) cells showed significant antileukemic activity, leading to complete remission in 4 out of 8 evaluable patients by day 28.

The ML NK cells expanded and persisted for over 3 months without significant toxicity, suggesting that this approach, combined with donor lymphocyte infusions, could be a promising new immunotherapy for relapsed AML in a post-transplant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. Bednarski, JJ., Zimmerman, C., Berrien-Elliott, MM., et al.[2023]

A GMP-compliant method was developed to expand alloreactive NK cells from healthy donors, achieving a 117-fold increase in NK cell numbers over 19 days, which is crucial for effective immunotherapy in acute myeloid leukemia (AML).

The expanded NK cells, particularly those with specific killer immunoglobulin-like receptor (KIR) profiles, demonstrated strong cytotoxicity against AML cells in vitro and reduced tumor load in vivo, indicating their potential for clinical use in NK cell-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients. Siegler, U., Meyer-Monard, S., Jörger, S., et al.[2020]

In a study testing CD33-CAR NK cells in patients with relapsed and refractory acute myeloid leukemia (AML), no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile.

CAR NK-92 cells can be produced at a lower cost than CAR T cells, indicating that with further optimization, they could become a more accessible treatment option for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Tang, X., Yang, L., Li, Z., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/136/Supplement%201/42/470631/A-Phase-1-Study-of-NKX101-an-Allogeneic-CAR

A Phase 1 Study of NKX101, an Allogeneic CAR Natural Killer ... Complete remission with or without hematologic recovery from 20% to 50% has been noted in patients with R/R AML with non-engineered, allogeneic ...

2. ir.nkartatx.com ir.nkartatx.com/news-releases/news-release-details/nkarta-updates-clinical-progress-car-nk-cell-therapy-nkx101

Nkarta Updates Clinical Progress of CAR-NK Cell Therapy ... This Phase 1 clinical trial evaluates the safety and anti-tumor activity of NKX101 as a multi-dose, multi-cycle cellular therapy following lymphodepletion in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548124/

CAR-T and CAR-NK cell therapies in AML For instance, CD123-directed CAR-T cells achieved complete remission (CR) in 50–66% of R/R AML patients, albeit with transient efficacy and ...

4. withpower.com withpower.com/trial/car-nk-cell-therapy-for-acute-myeloid-leukemia-or-myelodysplastic-syndrome-94f6d

CAR NK Cell Therapy for Acute Myeloid Leukemia or ... CAR NK cell therapy, including treatments like NKX101, has shown a favorable safety profile in early studies for acute myeloid leukemia (AML). In one study, no ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123087001

A Phase 1 Study of NKX101, a Chimeric Antigen Receptor ... Alternative LD with Flu/Ara-C followed by NKX101 shows promising early responses including MRD negativity in r/r AML. The toxicity profile of ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224009089

CAR-NK cell therapy in AML: Current treatment, challenges ... Pre-clinical studies utilizing CD33-targeted CAR NK cells for AML treatment demonstrate encouraging results.

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2097/500028/A-Phase-1-Study-of-NKX101-a-Chimeric-Antigen

A Phase 1 Study of NKX101, a Chimeric Antigen Receptor ... NKX101 is an NK cell therapy derived from healthy donors and engineered to express an NKG2D ligand-directed chimeric antigen receptor (CAR) to enhance killing ...