What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML), particularly those involving hematopoietic cell transplantation (HCT) with myeloablative conditioning, are associated with several side effects. These include severe hematologic toxicity (leukopenia, thrombocytopenia, anemia), gastrointestinal and hepatic toxicity, hemorrhagic complications, infectious complications, and pulmonary toxicity. Graft-versus-host disease (GVHD) is also a significant risk, although the use of ex-vivo expanded HLA-haploidentical donor natural killer (NK) cells aims to reduce this risk while facilitating immune reconstitution and decreasing relapse rates.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML) that involve immune modulation and targeted therapies. For instance, gemtuzumab ozogamicin (Mylotarg) is an antibody-drug conjugate targeting CD33, approved for newly diagnosed and relapsed AML. Additionally, midostaurin (Rydapt) targets FLT3 mutations and is used in combination with chemotherapy for newly diagnosed AML. While these treatments do not specifically involve NK cells, they represent the broader category of targeted and immune-modulating therapies that aim to improve outcomes in AML patients. The trial involving Ex-vivo Expanded HLA-haploidentical Donor Natural Killer (NK) Cells is a novel approach that builds on these principles by enhancing immune reconstitution and reducing relapse rates.

What other types of research exist?

Promising alternatives to Ex-vivo Expanded HLA-haploidentical Donor Natural Killer (NK) Cells for AML patients include CAR-T cell therapy and allogeneic hematopoietic cell transplantation (HCT). CAR-T cell therapy has shown efficacy in certain hematologic malignancies with a nonrelapse mortality (NRM) of less than 10 percent. Allogeneic HCT, particularly with matched sibling donors, has demonstrated reduced relapse rates and improved overall survival, although it comes with higher treatment-related mortality. Both therapies are being refined to enhance outcomes and reduce complications.

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NK Cell Infusions for Acute Myeloid Leukemia (EXCEL Trial)

Phase 2

Waitlist Available

Research Sponsored by Michael Pulsipher, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥ 500/mm3

Must not have

Prior allogeneic transplant

Active extramedullary disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to infusion such as fever or chills; increased risk of GVHD where the body attacks the new cells; possible infection risks due to immune suppression; and typical transplantation complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 25 years old or younger.

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I can take care of myself but may not be able to do active work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a transplant from a donor.

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My cancer has spread outside the bone marrow.

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I am currently fighting a serious infection that hasn't improved with treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

1-year RFS

Secondary study objectives

Cumulative incidence of neutrophil engraftment

Cumulative incidence of platelet engraftment

Graft-vs-Host Disease

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment ArmExperimental Treatment1 Intervention

All subjects will receive NK infusions.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Myeloid Leukemia (AML) include chemotherapy agents such as daunorubicin and cytarabine, which work by damaging the DNA of rapidly dividing cells, leading to cell death. This is crucial for reducing the number of leukemia cells in the body. Additionally, innovative therapies like ex-vivo expanded HLA-haploidentical donor natural killer (NK) cells are being studied. These NK cells are designed to enhance immune reconstitution, decrease relapse rates, and reduce infectious complications without increasing the risk of graft-versus-host disease (GVHD). This matters for AML patients as it offers a potential for improved survival rates and quality of life by targeting leukemia cells more effectively while minimizing adverse effects.

Clinical grade production of IL-15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post-transplant cyclophosphamide.Natural killer cells in acute myeloid leukemia patients: from phenotype to transcriptomic analysis.Natural killer cells generated from cord blood hematopoietic progenitor cells efficiently target bone marrow-residing human leukemia cells in NOD/SCID/IL2Rg(null) mice.