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Safety Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in COVID-19 pnEumonia or Lymphopenia (RELEASE)

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ClinicalTrials.gov Identifier: NCT04578210
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
Universidad Autonoma de Madrid
Universidad Miguel Hernandez de Elche
Biocruces Bizkaia Health Research Institute
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Information provided by (Responsible Party):
Instituto de Investigación Hospital Universitario La Paz

Brief Summary:

This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19.

Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state.

This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.


Condition or disease Intervention/treatment Phase
Corona Virus Infection Biological: T memory cells and NK cells Phase 1 Phase 2

Detailed Description:

In this phase I/II trial natural killer (NK) cells or memory T lymphocytes will be infused from donors who have recovered from COVID-19 and have complete resolution of symptoms for at least 14 days.

There will be two arms based on the biology of the donor and the patient:

  1. Infusion of NK cells which are cells of the innate immune system that can eliminate virally infected cells.
  2. Infusion of memory T cells which have the SARS-COV-2 memory T cell repertoire.

The investigators expect a quick recovery of the patients with pneumonia or lymphopenia for two reasons:

  1. NK cells act quickly after a viral infection. The number and function of NK cells correlates with the severity of another coronavirus infection, Severe Acute Respiratory Syndrome (SARS), originated in China in 2002.

    Moreover, the investigators have previous successful experience with other viruses such as CMV, EBV and HHV-6.

  2. The pool of memory T cells will increase in patients. Memory T cell levels are low in these patients. These lymphocytes have long-life memory, which upon reencountering SARS-CoV-2 will induce enhanced effector function resulting in greater protection of the patient.

Patients who have recovered from COVID-19 are the ideal donor candidates because they have immune cells with memory against SARS-CoV-2. Therefore, the infusion of NK and memory T cells from these donors will increase the pool of cells with cytotoxicity to virally infected cells, and will increase the pool of memory cells that respond quicker to a previously encountered stimulus.

This will impact in saving thousands of lives, releasing hospital beds, reducing the costs of a national health system and improving the economy of a locked-down country.

Cell therapies are safe and cost-effective and successfully used in other diseases. the investigators need new innovative treatments where others have failed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This Phase I/II escalating-dose clinical trial is a randomized study to determine safety, tolerability, alloreactivity and efficacy of cell therapy with adoptive cell therapy of NK cells or memory T cells in patients affected by COVID-19 Donors will be patientsrecovered from COVID-19 Will be 2 arms

  • A: allogeneic T memory cells
  • B: allogeneic NK cells

There will be two consecutive phases:

  • The first dose escalation focuses on determining safety and the recommended dose for the second segment Phase I: Patients with SARS-CoV-2+ pneumonia and/or lymphopenia and O2Sat ≤ 94% on room air at screening, with no oxygen required or with an oxygen need of ≤ 2.5 lpm in nasal cannula, will be selected This phase has a single ascending dose design with up to 3 planned dose levels for each arm
  • The second phase extends the safety study Phase II: Patients with SARS-CoV-2+ pneumonia and/or lymphopenia and O2Sat ≤ 94% on room air at screening, requiring or not oxygen supplementation
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I/II Dose-escalation Multi Center Study to Evaluate the Safety of Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in coronaviruS pnEumonia and/or Lymphopenia
Actual Study Start Date : September 4, 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: Arm A: allogeneic T memory cells
patients will receive memory T cells
Biological: T memory cells and NK cells
Single infusion of NK or memory T cells from a healthy donor recovered from COVID-19 (dose escalation).

Experimental: Arm B: allogeneic NK cells
patients will receive NK cells
Biological: T memory cells and NK cells
Single infusion of NK or memory T cells from a healthy donor recovered from COVID-19 (dose escalation).




Primary Outcome Measures :
  1. Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD [ Time Frame: 3 months ]
    Any grade 3 or higher toxicity with an attribution of definitely or probably related to the infusion of the cells and any lower grade toxicity that increases to a grade 3 or higher as a direct result of the cell infusion.



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Ages Eligible for Study:   up to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients ≤ 80 years of age.
  • Patient with diagnosis of COVID-19 infection with laboratory confirmation by reverse-transcription PCR (RT-PCR) of SARS-CoV-2 <72 hours prior to study entry.
  • Onset of symptoms < 10 days prior to administration of study treatment.
  • No more than 72 hours (3 days) of hospitalization before study treatment administration.
  • Phase I criteria: Patients requiring hospitalization for COVID-19, with pneumonia diagnosed with chest radiograph or computed tomography imaging or lymphopenia (absolute lymphocyte counts below 1.2 x 109cells /L) AND O2Sat ≤ 94% on room air at screening, no oxygen requirement or with an oxygen need of ≤ 2.5 lpm in nasal cannula.
  • Phase II criteria: Patients requiring hospitalization with pneumonia diagnosed with chest radiograph or computed tomography imaging or lymphopenia (absolute lymphocyte counts below 1.2 x 109cells /L) AND O2Sat ≤ 94% on room air at screening, requiring or not oxygen supplementation (nasal cannula, oxygen mask with reservoir, non-invasive ventilation, etc), but excluding mechanical ventilation.
  • Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
  • Be willing and able to comply with study procedures.
  • Patients with the ability to comprehend and sign the informed consent
  • Written informed consent obtained prior to any screening procedures.

Exclusion Criteria:

  • Enrolled in another Clinical Trial for COVID19.
  • Rapidly progressive disease with anticipated life-expectancy <72 hours.
  • Patients requiring mechanical ventilation.
  • Patients with multiorgan failure.
  • Mild-moderate (grade ≥ 3) organ impairment (liver, kidney, respiratory), according to criteria from the National Cancer Institute (NCI CTCAE version 5.0).
  • Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
  • Have a known history of human immunodeficiency virus infection, Hepatitis B or Hepatitis C; testing is not required in the absence of prior documentation or known history.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Any other condition that, in the opinion if the Investigator, may interfere with the efficacy and/or safety evaluation of the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04578210


Locations
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Spain
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Víctor Alelú Hernández, Mr    91 497 53 59    victor.alelu.ucicec@gmail.com   
Principal Investigator: Antonio Pérez Martínez, Dr         
Principal Investigator: Carlos Solano, Dr         
Principal Investigator: Cristina Eguizabal, Dra         
Principal Investigator: Bernat Soria, Dr         
Sponsors and Collaborators
Instituto de Investigación Hospital Universitario La Paz
Universidad Autonoma de Madrid
Universidad Miguel Hernandez de Elche
Biocruces Bizkaia Health Research Institute
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
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Responsible Party: Instituto de Investigación Hospital Universitario La Paz
ClinicalTrials.gov Identifier: NCT04578210    
Other Study ID Numbers: RELEASE
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lymphopenia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases