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LeukemiaPhase 1NCT05375253

Donor Enriched Activated NK Cell Infusion Post Haploidentical Stem Cell Transplant for Refractory Myeloid Malignancies

A Phase 1 study testing Donor Enriched Activated Natural Killer Cell Infusion in people with Leukemia, run by University of Nebraska.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Patients with relapse refractory myeloid malignancies have no therapeutic options for long term remission. Some success has been achieved in treating patients with refractory relapsed acute myeloid leukemia (AML) in using haploidentical cytokine activated natural killer (NK) cell immunotherapy. Read more about this study

Who is it for?
Ages 19 to 70 years
Conditions the study is for
Leukemia
What is being tested?
Donor Enriched Activated Natural Killer Cell Infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
12 Apr 2023to 12 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

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 19 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to understand and sign informed Consent
  • Age > 19 years and ≤ 70 years.
  • Deemed eligible for allogeneic stem cell transplantation with a minimum KPS of 70% (Appendix A).
  • Available HLA-haploidentical related donor as defined in section 5.2.1
  • Subjects with adequate organ functions as measured by:
  • Cardiac: Left ventricular ejection fraction at rest must be >45%,
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  • Hepatic: Bilirubin < 2.5 mg/dL except for Gilbert syndrome; and ALT, AST, and Alkaline Phosphatase < 5 x ULN.
  • Renal: GFR > 50 mL/min/1.73m2,
  • Pulmonary: FEV 1, FVC, DLCO ion capacity) > 45% predicted (corrected for hemoglobin); or 02 saturation > 92% on room air.
  • Able to be off of corticosteroids (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) and any other immune suppressive medications beginning on Day -3
  • Subjects with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebral spinal fluid (CSF) is clear for at least 2 weeks prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
  • Clinical diagnosis of one of the following:
  • Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one or more cycles of re-induction therapy. decitabine or azacytidine with venetoclax will be considered as one cycle of induction therapy.
  • Myelodysplastic Syndrome+/- myeloproliferative neoplasm MDS/MPN which failed to adequately respond (persistence of blasts >5%) to hypomethylating agents and or chemotherapy (minimum of 3 cycles of hypomethylating agents or 2 cycles of hypomethylating + venetoclax or one cycle of induction chemotherapy)

Who cannot join

  • Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
  • Circulating peripheral blood blast count > 1000/µl (despite hydroxyurea and or leukapheresis).
  • Previous allogeneic stem cell transplant.
  • Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of ≥5000 as assessed by the single antigen bead assay, < 6 weeks prior to starting transplant conditioning
  • Uncontrolled angina, severe uncontrolled ventricular arrhythmias.
  • Received any investigational drugs within the 14 days prior to the first day of transplant conditioning (starting on day -6)
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  • Women of child-bearing potential must not be pregnant and/or breastfeeding
  • Note: All females with intact ovaries and uterus will have two pregnancy tests as part of standard of care pre-transplant protocols.
  • Evidence of HIV infection or known HIV positive serology (completed as part of pre-transplant testing).
  • Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
  • Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.

About this study

Official title: A Phase I Trial of Donor Enriched Activated NK (DEA-NK) Cell Infusion Post Haploidentical Stem Cell Transplant for Refractory Myeloid Malignancies

Patients with relapse refractory myeloid malignancies have no therapeutic options for long term remission. Some success has been achieved in treating patients with refractory relapsed acute myeloid leukemia (AML) in using haploidentical cytokine activated natural killer (NK) cell immunotherapy. This process infuses natural killer (NK) cells from a half- or partially-matched donor. These cells are a type of lymphocytes made by a person's immune system that are important for fighting infection and tumor cells and are modified with other immune system substances to be more effective. One limiting factor is the recovery of recipient's immune system rejecting the infused NK cells. The use of haploidentical activated NK cell therapy post-transplant is a possible option to create longer lived infused NK cells and support cancer fighting ability.

Read the detailed description

Patients with relapse refractory myeloid malignancies [acute myeloid leukemia (AML) myelodysplastic (MDS)/myeloproliferative (MPD) disorders] have no therapeutic options for long term remission. Haploidentical cytokine activated natural killer (NK) cell immunotherapy has been used with some success in treating patients with refractory relapsed AML. One limiting factor to the in-vivo expansion of infused activated NK cells is the recovery of recipient's immune system rejecting the infused NK cells. The use of haploidentical activated NK cell therapy post haploidentical transplant is an attractive option to induce in-vivo persistence of the infused NK cells and support anti leukemic efficacy.

This is a pilot trial testing the feasibility, safety and immunologic effects of dose escalated donor enriched activated natural killer cell infusion (DEA-NK) on day +7 post haploidentical stem cell transplantation. Participants must be adult patients with relapse refractory AML, MDS, or MPD, available haploidentical related donor, and adequate organ functions to undergo stem cell transplant. Participants will be followed for 6 months and 1 year following transplant.

Conditions
Leukemia
Being tested
Donor Enriched Activated Natural Killer Cell Infusion
Medical subject headings
Leukemia

What participants receive

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

  • Donor Enriched Activated Natural Killer Cell InfusionBiological

    αβ TCR/CD19 depleted (DEA-NK) cells on day +7 post T-cell replete Haplo-Tx with PTCY

Study groups in NCT05375253
Study groupRoleWhat they receive
Donor Enriched Activated NK Infusion (DEA-NK)ExperimentalInfusion of DEA-NK on day +7 post-transplant
Receives: Biological: Donor Enriched Activated Natural Killer Cell Infusion

What is being measured

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

  1. Percent of successful DEA-NK cell infusions

    Assess the feasibility of infusing activated enriched donor natural killer cell infusion (DEA-NK) at day +7 post-transplant by the ability to manufacture and administer the DEA-NK cells at study dose levels.

    Measured: 100 Days

  2. Number of adverse events for those who have a DEA-NK cell infusion

    Assess safety of the DEA-NK cell infusions by recording adverse events experienced by subjects at each dose level.

    Measured: 100 Days

  3. Maximum tolerated dose of DEA-NK cell infusions

    To determine the maximum tolerated dose (MTD) of DEA-NK cell infusion as determined by dose limiting toxicities (DLT) observed.

    Measured: 100 Days

Secondary outcomes (4)

  1. Non-Relapse Mortality Rate

    Non-Relapse Mortality (NRM) at 100 days, 180 days and 1 year

    Measured: 1 year

  2. Time to neutrophil recovery

    Time to neutrophil recovery defined as the first of 3 consecutive days following the nadir that the absolute neutrophil count is at least 500/µl

    Measured: 21 Days

  3. Time to platelet recovery

    Time to platelet recovery defined as the first day that the platelet count is at least 20,000/µl without a transfusion in the preceding 7 days

    Measured: 21 Days

  4. Incidence of graft failure

    Incidence of graft failure as defined by ANC < 500/µl by Day +35 in the absence of disease recurrence

    Measured: 35 Days

Timeline

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

  1. First posted16 May 2022
  2. Study start12 Apr 2023
  3. Primary completion12 Apr 2023
  4. Study completion12 Apr 2023

Why it stopped: PI has left institution and is taking the study with him.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05375253
Sponsor's protocol ID
0158-22-FB
Status last verified
Aug 2024
First submitted
10 May 2022
Last updated
3 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Donor Enriched Activated Natural Killer Cell Infusion in people with Leukemia, run by University of Nebraska.

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 14 inclusion and 11 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: withdrawn, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Percent of successful DEA-NK cell infusions (time frame: 100 Days). The study lists 3 primary outcomes in all. 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 NCT05375253.

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 3 Sep 2024.

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