NK Cell Infusions for Acute Myeloid Leukemia

(EXCEL Trial)

Recruiting at 14 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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if giving special immune cells from a donor to children and young adults with high-risk AML can help their immune system fight cancer and infections better after a bone marrow transplant.

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 data supports the effectiveness of the treatment Ex-Vivo Expanded Natural Killer Cell Infusions for Acute Myeloid Leukemia?

Research shows that natural killer (NK) cells have strong antileukemia properties, and studies have demonstrated that infusing these cells can help some patients achieve remission. In one study, 4 out of 8 patients with relapsed acute myeloid leukemia achieved complete remission after receiving memory-like NK cells, indicating the potential effectiveness of NK cell infusions. ^{1 2 3 4 5}

Is NK cell infusion safe for humans?

Research shows that NK cell infusions have been used safely in humans, including children and elderly patients with acute myeloid leukemia (AML). Studies report no significant toxicity, suggesting that NK cell infusions are generally safe for human use. ^{1 3 6 7 8}

How does the NK cell infusion treatment for acute myeloid leukemia differ from other treatments?

NK cell infusion for acute myeloid leukemia is unique because it uses natural killer (NK) cells that are activated and expanded to target leukemia cells, offering a novel immunotherapy approach. Unlike traditional chemotherapy, this treatment leverages the body's immune system to fight cancer, potentially with fewer side effects. ^{1 3 4 7 9}

Research Team

Michael L Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

The antileukemic potential of natural killer cells. [2016]

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. China pubmed.ncbi.nlm.nih.gov

[Cytotoxicity of allogenetic natural killer cells against CD34+ acute myelogenous leukemia cells]. [2008]

5. Germany pubmed.ncbi.nlm.nih.gov

Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation. [2020]

6. China 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]. [2022]

7. Germany 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Evaluation of ex vivo expanded human NK cells on antileukemia activity in SCID-beige mice. [2019]

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

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