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

NCT04578210 | Completed Phase 1 DMC

• 1 other identifier: RELEASE
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Corona Virus Infection

Outcome Measures

Primary Outcomes (2)

• Phase I: Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD

  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.

  3 months

• Phase II

  Phase II primary outcome is the incidence of patient recovery infusing adoptive NK cells or adoptive memory T cells. Recovery is defined as the proportion of participants in each group with normalization of fever and oxygen saturation (criteria for normalization: temperature \< 38°C armpit, and SpO2 \> 94%, sustained for at least 24 h) or lymphopenia recovery through day 14.

  3 months

Secondary Outcomes (1)

• Secondary Outcomes

  3 months

Other Outcomes (1)

• Exploratory Outcomes

  3 months

Study Arms (2)

Arm A: allogeneic T memory cells

EXPERIMENTAL

patients will receive memory T cells

Biological: T memory cells and NK cells

Arm B: allogeneic NK cells

EXPERIMENTAL

patients will receive NK cells

Biological: T memory cells and NK cells

Interventions

T memory cells and NK cells BIOLOGICAL

Single infusion of NK or memory T cells from a healthy donor recovered from COVID-19 (dose escalation).

Arm A: allogeneic T memory cells; Arm B: allogeneic NK cells

Eligibility Criteria

• Age: Up to 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead
• Universidad Autonoma de Madrid: collaborator
• Universidad Miguel Hernandez de Elche: collaborator
• Biobizkaia Health Research Institute: collaborator
• Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana: collaborator

Study Sites (1)

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (5)

• Ferreras C, Hernandez-Blanco C, Martin-Quiros A, Al-Akioui-Sanz K, Mora-Rillo M, Ibanez F, Diaz-Almiron M, Cano-Ochando J, Lozano-Ojalvo D, Jimenez-Gonzalez M, Goterris R, Sanchez-Zapardiel E, de Paz R, Guerra-Garcia P, Queiruga-Parada J, Molina P, Briones ML, Ruz-Caracuel B, Borobia AM, Carcas AJ, Planelles D, Vicario JL, Moreno MA, Balas A, Llano M, Llorente A, Del Balzo A, Canada C, Garcia MA, Calvin ME, Arenas I, Perez de Diego R, Eguizabal C, Soria B, Solano C, Perez-Martinez A. Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210). Cytotherapy. 2024 Jan;26(1):25-35. doi: 10.1016/j.jcyt.2023.10.002. Epub 2023 Oct 29.

  PMID: 37897472 DERIVED

• Herrera L, Martin-Inaraja M, Santos S, Ingles-Ferrandiz M, Azkarate A, Perez-Vaquero MA, Vesga MA, Vicario JL, Soria B, Solano C, De Paz R, Marcos A, Ferreras C, Perez-Martinez A, Eguizabal C. Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy. Immunology. 2022 Feb;165(2):234-249. doi: 10.1111/imm.13432. Epub 2021 Dec 2.

  PMID: 34775592 DERIVED

• Garcia-Garcia I, Guerra-Garcia P, Ferreras C, Borobia AM, Carcas AJ, Queiruga-Parada J, Vicario JL, Mirones I, Solano C, Eguizabal C, Soria B, Perez-Martinez A. 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: RELEASE study protocol. Trials. 2021 Oct 2;22(1):674. doi: 10.1186/s13063-021-05625-7.

  PMID: 34600562 DERIVED

• Perez-Martinez A, Mora-Rillo M, Ferreras C, Guerra-Garcia P, Pascual-Miguel B, Mestre-Duran C, Borobia AM, Carcas AJ, Queiruga-Parada J, Garcia I, Sanchez-Zapardiel E, Gasior M, De Paz R, Marcos A, Vicario JL, Balas A, Moreno MA, Eguizabal C, Solano C, Arribas JR, Buckley RM, Montejano R, Soria B. Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE). EClinicalMedicine. 2021 Sep;39:101086. doi: 10.1016/j.eclinm.2021.101086. Epub 2021 Aug 13.

  PMID: 34405140 DERIVED

• Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.

  PMID: 33811823 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I/II escalating-dose clinical trial, 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 patients recovered from COVID-19 Will be 2 arms * A: allogeneic T memory cells * B: allogeneic NK cells Two consecutive phases: * The first dose escalation focuses on determining safety and the recommended dose for the phase II 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

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: September 4, 2020
• Primary Completion: January 13, 2022
• Study Completion: March 30, 2022
• Last Updated: June 1, 2023

Record last verified: 2022-05

Locations

ES (1)