NK Cell Infusions for Acute Myeloid Leukemia

(EXCEL Trial)

Enrolling by invitation at 15 trial locations

Overseen By Cindy Zhuang

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Michael Pulsipher, MD

Disqualifiers: Active infection, Pregnancy, Prior transplant, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using natural killer (NK) cells to aid children and young adults with high-risk acute myeloid leukemia (AML). The goal is to determine if NK cell infusions can help the immune system recover, reduce the risk of cancer recurrence, and prevent infections without increasing side effects. The trial targets those who have had AML for some time or possess certain high-risk features, such as specific genetic mutations. Participants should have recovered from prior chemotherapy, maintaining stable health while still battling AML. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team to get a clear answer.

What prior data suggests that this treatment is safe for children and young adults with acute myeloid leukemia?

Research has shown that adoptive natural killer (NK) cell therapy is generally safe for people with acute myeloid leukemia (AML). Past studies reported no serious side effects from NK cell infusions, indicating that patients tolerate this treatment well. Specifically, the NK cell administration itself caused no harmful effects. Additionally, NK cell therapy has proven safe for patients with difficult-to-treat AML. These findings support its use as a promising treatment for improving patient outcomes without adding significant risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Unlike the standard treatments for acute myeloid leukemia, which often involve chemotherapy and stem cell transplants, NK cell infusions offer a unique approach by using natural killer cells to fight cancer. These cells are a type of immune cell that can target and destroy cancer cells without harming normal cells. Researchers are excited because NK cell infusions could potentially enhance the body's natural immune response to leukemia, providing a more targeted and potentially less toxic treatment option. This innovative method could lead to better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that NK cell infusions might be an effective treatment for acute myeloid leukemia?

Research has shown that NK (natural killer) cell therapy may help treat acute myeloid leukemia (AML). Patients receiving NK cells after a transplant experienced fewer relapses. These cells aid the immune system in recovery and cancer defense. Studies also suggest that NK cell therapy can reduce infection risk without increasing the chance of graft-versus-host disease (GVHD), a common post-transplant issue. Overall, researchers are studying NK cell infusions as a promising method to improve survival rates in high-risk AML patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Michael L Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 25 years old with high-risk acute myeloid leukemia (AML) who are undergoing a specific bone marrow transplant. They must have certain genetic mutations or minimal residual disease, be recovering from chemotherapy, and have good performance status and organ function. Those with Fanconi Anemia, Down syndrome, active extramedullary disease, serious infections, or prior transplants cannot join.

Inclusion Criteria

My white blood cell count is healthy following my last chemotherapy.

Adequate major organ system function as demonstrated by: Renal: Creatinine clearance (CrCl) ≥60 mL/min/1.73m2 by Cockcroft-Gault formula, Schwartz formula, or nuclear GFR study (Table 3) Hepatic: Total bilirubin <2 mg/dL (unless due to Gilbert syndrome) and ALT and AST < 5x ULN Cardiac: LVEF at rest ≥50% or SF ≥27% (by MUGA or ECHO) Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For patients <7 years of age or those unable to perform PFTs: O2 Sat >92% on room air by pulse oximetry and on no supplemental O2 at rest

The patient, patient's parent, guardian, or legal representative can provide written informed consent

Exclusion Criteria

I have had a transplant from a donor.

You have either Fanconi Anemia or Down syndrome.

My cancer has spread outside the bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplant

Participants undergo a myeloablative conditioning regimen with busulfan and cyclophosphamide, followed by HLA-haploidentical hematopoietic cell transplant

2-3 weeks

NK Cell Infusion

Participants receive three fixed dose infusions of ex-vivo expanded NK cells

3 weeks

Follow-up

Participants are monitored for safety, GVHD incidence, and immune reconstitution

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ex-Vivo Expanded Natural Killer Cell Infusions

Trial Overview The study tests the effect of three doses of donor-derived natural killer cell infusions on patients with high-risk AML receiving a special bone marrow transplant. The goal is to see if these infusions help rebuild the immune system, lower relapse rates without increasing graft versus host disease (GVHD), leading to better survival rates.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

All subjects will receive NK infusions.

Who Is Running the Clinical Trial?

Michael Pulsipher, MD

Lead Sponsor

Trials

5

Recruited

240+

Michael Pulsipher

Lead Sponsor

Trials

1

Recruited

60+

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

A trifunctional natural killer cell engager (NKCE) has been developed that specifically targets and kills CD123+ acute myeloid leukemia (AML) cells, showing promise as a potential treatment for this type of cancer.

This NKCE represents a novel approach to harnessing the body's immune system to fight leukemia, which could lead to more effective therapies for patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Trifunctional Natural Killer Cell Engager Can Target CD123+ Leukemia. [2023]

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]

The study involved 40 elderly patients with acute myeloid leukemia (AML), showing that donor NK cell infusions are generally safe, with only mild side effects like moderate fever occurring in a few cases after multiple infusions.

High-purity NK cells were successfully expanded and transfused, with no cases of acute graft-versus-host disease (GVHD) observed in elderly AML patients, indicating a promising safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Safety of NK Cell in the Prevention of Leukemia Relapse Post-transplantation and in Treatment of the Elderly Leukemia Patients]. Liu, J., Zheng, XL., Xue, M., et al.[2022]

Adoptive NK cell infusion using clinical-grade membrane-bound IL-21/4-1BBL-expanded NK cells showed significant antileukemic activity against acute myeloid leukemia (AML) in both laboratory and animal studies, with expanded NK cells persisting in the body for at least 13 days after infusion.

Patients with minimal residual disease (MRD+) who received NK cell treatment experienced better overall survival compared to those undergoing standard consolidation therapy, with no major adverse events reported, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded clinical-grade membrane-bound IL-21/4-1BBL NK cell products exhibit activity against acute myeloid leukemia in vivo. Zhao, XY., Jiang, Q., Jiang, H., et al.[2021]

In a phase I/II trial involving 24 acute myeloid leukemia patients, haploidentical stem cell transplantation combined with early transfer of unmodified NK cells resulted in a promising 2-year overall survival rate of 37%.

The study demonstrated that transferred NK cells not only proliferated in the patients' bodies without needing additional IL-2 but also showed a mature phenotype, suggesting that this approach could enhance the effectiveness of treatment against high-risk leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation. Killig, M., Friedrichs, B., Meisig, J., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11748472/

Adoptive NK cell therapy in AML: progress and challenges Our review highlights the significant potential of NK cell-based therapies for AML, while addressing the technical and biological challenges ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04347616

Natural Killer-cell Therapy for Acute Myeloid Leukemia This study investigates an innovative treatment for relapsed or refractory acute myeloid leukemia exploiting administration of ex vivo-generated allogeneic ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2452318625000431

Immunotherapy with ex vivo–expanded donor-derived NK ... NK cell therapy has shown potential as a relapse-prevention strategy in high-risk patients with AML undergoing haploidentical HSCT.

4. 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 ... This study aimed to systematically review clinical trials utilizing NK cell-based treatments for AML in pediatric and adult populations, ...

5. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/12713/493017/Higher-Dose-Donor-Derived-Ex-Vivo-Expanded-Natural

Higher-Dose Donor Derived Ex Vivo Expanded Natural Killer ... Adoptive immunotherapy with donor-derived natural killer (NK) cell was deemed as a promising therapeutic in hematological malignancies with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04836390

Study Details | NCT04836390 | Donor-Derived Ex-Vivo ... This is a Phase II pilot study to determine the efficacy of three fixed dose (1 x 108/kg) infusions of ex-vivo expanded human leukocyte antigen ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT411662

Clinical-grade natural killer cells expanded from donor ... It has been reported that allogeneic NK cell therapy has good safety and curative effect in patients with refractory and relapsed acute myeloid leukemia (AML).