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

August 29, 2024 updated by: University of Nebraska

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Able to understand and sign informed Consent
  2. Age > 19 years and ≤ 70 years.
  3. Deemed eligible for allogeneic stem cell transplantation with a minimum KPS of 70% (Appendix A).
  4. Available HLA-haploidentical related donor as defined in section 5.2.1

  5. Subjects with adequate organ functions as measured by:

    1. Cardiac: Left ventricular ejection fraction at rest must be >45%,
    2. Hepatic: Bilirubin < 2.5 mg/dL except for Gilbert syndrome; and ALT, AST, and Alkaline Phosphatase < 5 x ULN.
    3. Renal: GFR > 50 mL/min/1.73m2,
    4. Pulmonary: FEV 1, FVC, DLCO ion capacity) > 45% predicted (corrected for hemoglobin); or 02 saturation > 92% on room air.
  6. 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
  7. 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.
  8. Clinical diagnosis of one of the following:

A. 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.

B. 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)

Exclusion Criteria:

  1. Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
  2. Circulating peripheral blood blast count > 1000/µl (despite hydroxyurea and or leukapheresis).
  3. Previous allogeneic stem cell transplant.
  4. 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
  5. Uncontrolled angina, severe uncontrolled ventricular arrhythmias.
  6. Received any investigational drugs within the 14 days prior to the first day of transplant conditioning (starting on day -6)

  7. Women of child-bearing potential must not be pregnant and/or breastfeeding

    a. Note: All females with intact ovaries and uterus will have two pregnancy tests as part of standard of care pre-transplant protocols.

  8. Evidence of HIV infection or known HIV positive serology (completed as part of pre-transplant testing).
  9. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
  10. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Donor Enriched Activated NK Infusion (DEA-NK)
Infusion of DEA-NK on day +7 post-transplant
Biological: Donor Enriched Activated Natural Killer Cell Infusion
αβ TCR/CD19 depleted (DEA-NK) cells on day +7 post T-cell replete Haplo-Tx with PTCY

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent of successful DEA-NK cell infusions
Time Frame: 100 Days
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.
100 Days
Number of adverse events for those who have a DEA-NK cell infusion
Time Frame: 100 Days
Assess safety of the DEA-NK cell infusions by recording adverse events experienced by subjects at each dose level.
100 Days
Maximum tolerated dose of DEA-NK cell infusions
Time Frame: 100 Days
To determine the maximum tolerated dose (MTD) of DEA-NK cell infusion as determined by dose limiting toxicities (DLT) observed.
100 Days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Non-Relapse Mortality Rate
Time Frame: 1 year
Non-Relapse Mortality (NRM) at 100 days, 180 days and 1 year
1 year
Time to neutrophil recovery
Time Frame: 21 Days
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
21 Days
Time to platelet recovery
Time Frame: 21 Days
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
21 Days
Incidence of graft failure
Time Frame: 35 Days
Incidence of graft failure as defined by ANC < 500/µl by Day +35 in the absence of disease recurrence
35 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nebraska

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zaid Al-Kadhimi, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 12, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 12, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 12, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 10, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0158-22-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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