CAR NK Cell Therapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome

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

61 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment NKX101 for acute myeloid leukemia or myelodysplastic syndrome?

Research shows that natural killer (NK) cells, which are part of the immune system, have strong anti-leukemia properties and can help fight acute myeloid leukemia (AML). Studies have demonstrated that enhancing NK cells with specific receptors can improve their ability to target and destroy leukemia cells, suggesting potential effectiveness for treatments like NKX101. ^{1 2 3 4 5}

Is CAR NK cell therapy safe for humans?

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 significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting it may be safer than similar therapies like CAR T cells. ^{1 2 6 7 8}

How is the treatment NKX101 unique for acute myeloid leukemia or myelodysplastic syndrome?

NKX101 is a novel treatment that uses CAR-NK cells, which combine the targeting ability of CAR technology with the natural tumor-killing function of NK cells, offering a potentially safer and more effective option compared to traditional CAR-T cell therapies, as it avoids severe side effects like graft-versus-host disease. ^{1 2 4 7 9}

What is the purpose of this trial?

This is a single-arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS.

Research Team

David Shook, MD

Principal Investigator

Nkarta, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Memory-like NK cells armed with a neoepitope-specific CAR exhibit potent activity against NPM1 mutated acute myeloid leukemia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

An overview of the potential strategies for NK cell-based immunotherapy for acute myeloid leukemia. [2018]

5. England 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. [2020]

6. United States 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

CAR-NK cells for acute myeloid leukemia immunotherapy: past, present and future. [2023]

8. Iran pubmed.ncbi.nlm.nih.gov

Hsp70, in Combination with IL-15 and PD-1 Blocker, Interferes with The Induction of Cytotoxic NK Cells in Relapsed Acute Myeloid Leukemia Patients. [2023]

9. China pubmed.ncbi.nlm.nih.gov

[Research Progress of Chimeric Antigen Receptor Modified NK Cells in the Treatment of Acute Myeloid Leukemia --Review]. [2023]