AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2EXCELNCT04836390

Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant

A Phase 2 study testing Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in people with Acute Myeloid Leukemia, run by Michael Pulsipher at 13 sites in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

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 (HLA)-haploidentical donor natural killer (NK) cells (haploNK) in children and young adults with high risk acute myeloid leukemia (AML) undergoing HLA-haploidentical… Read more about this study

Who is it for?
Ages 0 to 25 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
13 sitesUnited States
Study dates
24 Aug 2021to May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age ≤ 25 years at time of enrollment
  • High-risk AML, as defined by one of the following:
  • AML in CR1 (defined as <5% blasts in BM by morphology and flow cytometry) having at least one of these high-risk features:
  • Mutations associated with high risk disease (Appendix A). Other high-risk features not explicitly stated in Appendix A can be considered after discussion/approval with the protocol chair/team
  • MRD-positive at the end of Induction I chemotherapy (defined as flow cytometry ≥ 0.1% blasts)
  • AML in ≥CR2 (defined by <5% blasts in BM by morphology and flow cytometry)
Show all 15Show fewer
  • Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥ 500/mm3
  • AML secondary to select germline marrow failure disorders (with exception of Fanconi Anemia) may be eligible but require approval from Protocol Chairs prior to enrollment.
  • Performance status ≥70% (Lansky for <16 years; Karnofsky for ≥16 years)
  • 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

Who cannot join

  • Active extramedullary disease
  • Unresolved/ongoing and serious viral, bacterial, or fungal infection despite appropriate treatment
  • Positive pregnancy test in a female of child-bearing potential (FCBP)
  • Inability to comply with medical therapy or follow-up
  • Prior allogeneic transplant
  • Patients with Fanconi Anemia and Down syndrome

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

13 sites in 1 country

United States13 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Ann & Robert H. Lurie Children's Hospital

    Chicago, Illinois, 60611

  • Cleveland Clinic Lerner College of Medicine

    Cleveland, Ohio, 44195

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 95109

  • Washington University, St. Louis

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • New York Medical College

    Valhalla, New York, 10595

Other trials in United States

About this study

Official title: A Phase II Pilot Study of Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant: A Multicenter Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) Study

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 (HLA)-haploidentical donor natural killer (NK) cells (haploNK) in children and young adults with high risk acute myeloid leukemia (AML) undergoing HLA-haploidentical hematopoietic cell transplant (haploHCT) with a busulfan and cyclophosphamide-based myeloablative conditioning regimen and post-transplant cyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. The investigators will also demonstrate the feasibility of performing this trial in a multi-center study.

The investigators hypothesize that the infusion of haploNK in this setting will facilitate immune reconstitution and decrease relapse rates and infectious complications without increasing GVHD, resulting in improved survival as compared to recent historical cohorts of haploHCT without NK cell infusion.

Being tested
Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor-Derived Ex-Vivo Expanded Natural Killer Cell InfusionsDrug

    Peripheral blood (PB) ≤ 450 mL and based on donor weight (minimum 10 ml/kg) will be drawn from the HLA-haploidentical donor at least 16 days before the scheduled day of transplant (Day 0). HaploNK cells will be manufactured from the PB of the donor after co-culture with irradiated feeder cells (IFC) as described in Section 2.4. The recipients will receive three NK cell infusions on Day-1, Day+7 (± 1 day) and Day+42 (up to Day+90) from day of transplant (Day 0).

Study groups in NCT04836390
Study groupRoleWhat they receive
Treatment ArmExperimentalAll subjects will receive NK infusions.
Receives: Drug: Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1-year RFS

    The proportion and corresponding 95% exact binomial CI of patients who are relapse-free at 1-year from day of transplant (Day 0)

    Measured: 1 year

Secondary outcomes (6)

  1. Number of functional donor-derived NK cells generated from the device

    Product manufacturing failure is defined as inability to generate sufficient NK cell product due to failure to meet release criteria or insufficient cells for at least one full dose (≤10^8/NK cells/kg ABW).

    Measured: 2 years

  2. GVHD incidence

    The incidence of Grade II- IV aGVHD (Day +100) and cGVHD (Day+180, +1 year), opportunistic infections (+1 year), and OS (+1 year and +2 year).

    Measured: 2 years

  3. KIR ligand-ligand mismatch

    The presence of KIR ligand-ligand mismatch between HLA-haploidentical donor and host and the impact on relapse rate.

    Measured: 2 years

  4. Incidence of mixed donor chimerism

    Mixed donor chimerism is defined as >5%, but <95%, donor cells detected. Full donor chimerism is defined as >95% donor.

    Measured: 2 years

  5. Cumulative incidence of neutrophil engraftment

    The cumulative incidence of neutrophil engraftment from the time of transplant will be estimated using the cumulative incidence function with death and relapse prior to engraftment as the competing risk. The definition of neutrophil engraftment is a post-nadir ANC > 500/mm3 for three consecutive laboratory values obtained on different days. The first of the three days will be designated as the day of neutrophil recovery.

    Measured: 2 years

  6. Cumulative incidence of platelet engraftment

    The cumulative incidence of platelet engraftment from the time of transplant will be estimated using the cumulative incidence function with death and relapse prior to engraftment as the competing risk. The definition of platelet engraftment is sustained platelet count > 20,000/mm3 with no platelet transfusions in the preceding seven days. The first of three consecutive measurements on different days will be designated as the day of initial platelet recovery.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start24 Aug 2021
  3. Primary completionMay 2026 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04836390
Sponsor's protocol ID
CHLA-20-00314
Acronym
EXCEL
Status last verified
Nov 2024
First submitted
18 Mar 2021
Last updated
4 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data analysis and protocol can be made available to researchers upon request after publication.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in people with Acute Myeloid Leukemia, run by Michael Pulsipher at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1-year RFS (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04836390.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in