CD5CAR-NK Cells for Refractory Invasive Mold Disease (CD5CAR-NK)

Off-the-shelf CD5CAR-NK Cells for Refractory Invasive Mold Disease: Phase I Clinical Trial.

CD5CAR-NK is a first-in-human, pilot, dose-escalation, and single-site study to evaluate the safety of CD5CAR-CBNK in patients with invasive mold diseases (IMD).

The study population consists of patients aged ≥18 years with refractory mold infections.

The number of patients treated will be 10. This is a dose-escalation study including 3 cohorts.

Study Overview

• Status: Not yet recruiting
• Conditions: Fungal Infection
• Intervention / Treatment: Genetic: CD5CAR-CBNK

Detailed Description

CD5CAR-NK is a first-in-human, pilot, dose-escalation, and single-site study to evaluate the safety of CD5CAR-CBNK in patients with invasive mold diseases (IMD).

The study population consists of patients aged ≥18 years with refractory mold infections.

The number of patients treated will be 10.

This is a dose-escalation study including 3 cohorts. The dose escalation scheme will follow the following scheme:

Cohort 1(3 patients) The sentinel patient of cohort 1 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at day 0. Intra-patient safety will be reviewed daily following the first dose. The second dose (day+3) and third (day+6) will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

Cohort 1 is planned to include 3 evaluable patients. If a patient does not receive the full planned dosing schedule (all 3 doses), additional patients will be enrolled until at least 3 patients have completed the full prescribed treatment for this cohort. Escalation to Cohort 2 will only occur once safety data from 3 fully-treated patients have been reviewed.

The first subject in each cohort will be dosed and undergo a safety observation period between administrations. The second subject will be dosed 7 days after the first subject completes treatment and after review of safety data. The third subject will be dosed 3 days after the last dose of the second subject, subject to confirmation of acceptable safety.

Cohort 2 (3 patients) The sentinel patient of cohort 2 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12. Intra-patient safety will be reviewed daily following the first 25 million dose. The dose at day +12 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

Cohort 3 (4 patients) The sentinel patient of cohort 3 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12, and additionally 50 x106 CAR+ cells at days 15 and 18. In this occasion, intra-patient safety will be reviewed daily following the first 50 million dose. The dose at day +18 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maria Joyera; Phone Number: +34932775400; Email: joyera@recerca.clinic.cat
• Study Contact Backup: Name: Carolina Garcia Vidal, Dr.; Phone Number: +34932775400; Email: cgarciav@clinic.cat

Study Locations

• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08036
      • Hospital Clinic Barcelona
      • Contact: Carolinia Garcia Vidal, Dr.; Phone Number: +34932275400; Email: cgarciav@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.

2. Diagnosis of probable or proven fungal infection according to EORTC criteria20, who have been treated with the best available antifungal strategy and present at least one of the following criteria indicating inadequate response to antifungal therapy: Increase in fungal infection biomarker levels (serum or bronchoalveolar lavage galactomannan, or serum β-D-glucan) after at least one week of antifungal therapy:

   1. Persistence of positive cultures despite having received ≥2 weeks of appropriate antifungal treatment.
   2. Radiological worsening of lesions suggestive of fungal infection despite having received ≥2 weeks of appropriate antifungal treatment, and when at least 2 weeks have passed since the previous imaging study.
   3. Clinical deterioration and microbiological isolation of a fungus resistant to all available antifungal treatments (including cases in which a specific antifungal cannot be administered due to the risk of unacceptable toxicity).
   4. Rapidly progressive clinical deterioration despite the implementation of all available antifungal measures, conferring a poor prognosis for the patient.
3. Signing the informed consent form to participate in the clinical trial and to receive CD5CAR-CBNK therapy. If the patient is not in a condition to sign the informed consent form, consent will be requested from the family and patient consent for the study continuation will be obtained as soon as deemed possible.

Exclusion Criteria:

1. An expected survival of less than four weeks due to a cause unrelated to the current fungal infection.
2. Patients with positive HIV serology.
3. Pregnant or breastfeeding women.
4. Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; The sentinel patient of cohort 1 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at day 0. Intra-patient safety will be reviewed daily following the first dose. The second dose (day+3) and third (day+6) will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs). Cohort 1 is planned to include 3 evaluable patients. The first subject in each cohort will be dosed and undergo a safety observation period between administrations. The second subject will be dosed 7 days after the first subject completes treatment and after review of safety data. The third subject will be dosed 3 days after the last dose of the second subject, subject to confirmation of acceptable safety.	Genetic: CD5CAR-CBNK; Allogeneic natural killer (NK) cells derived from umbilical cord blood (CB) units, genetically modified to express a chimeric antigen receptor (CAR) based on the CD5 receptor (CD5CAR).
Experimental: Cohort 2; The sentinel patient of cohort 2 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12. Intra-patient safety will be reviewed daily following the first 25 million dose. The dose at day +12 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).	Genetic: CD5CAR-CBNK; Allogeneic natural killer (NK) cells derived from umbilical cord blood (CB) units, genetically modified to express a chimeric antigen receptor (CAR) based on the CD5 receptor (CD5CAR).
Experimental: Cohort 3; The sentinel patient of cohort 3 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12, and additionally 50 x106 CAR+ cells at days 15 and 18. In this occasion, intra-patient safety will be reviewed daily following the first 50 million dose. The dose at day +18 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).	Genetic: CD5CAR-CBNK; Allogeneic natural killer (NK) cells derived from umbilical cord blood (CB) units, genetically modified to express a chimeric antigen receptor (CAR) based on the CD5 receptor (CD5CAR).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety of allogeneic CD5CAR-CBNK cells in patients with refractory mold infection.	Number and proportion of patients with grade 3-4 treatment-related adverse events according to the Common Toxicity Criteria (CTCAE) version 5.0	28 days following the first infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety and tolerability of CD5CAR-CBNK cells.	Incidence of all grade >3 adverse events (AEs) as per CTCAE version 5.0.	at 6 and 12 weeks
Evaluate the safety and tolerability of CD5CAR-CBNK cells.	Number and percentage of patients with Adverse Events of Special Interest (AESI) throughout the study duration. The following AEs will be considered as AESI: i. Cytokine release syndrome (CRS) ii. Immune effector cell-associated neurotoxicity syndrome (ICANS) iii. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IEC-HS) iv. Prolonged cytopenia.	at 6 and 12 weeks
Evaluate the safety and tolerability of CD5CAR-CBNK cells.	Procedure-related mortality rate (PRM), defined as any death not related to the underlying disease or fungal infection.	During the first year after first administration
Evaluate the safety and tolerability of CD5CAR-CBNK cells.	Number and proportion of patients with grade 3-4 treatment-related adverse events according to the Common Toxicity Criteria (CTCAE) version 5.0	During the first year after first administration
Evaluate the safety and tolerability of CD5CAR-CBNK cells.	Number and percentage of patients with Serious Adverse Events (SAEs) according to CTCAE version 5.0.	During the first year after first administration
Assess the efficacy of CD5CAR-CBNK cells.	Response rate	at day 15, day 28, 6 and 12 weeks.
Assess the efficacy of CD5CAR-CBNK cells.	Overall Survival (OS)	at day 28, 6 and 12 weeks from the first CD5CAR-CBNK cell infusion and from study inclusion.
Assess the efficacy of CD5CAR-CBNK cells.	Survival rate	at day 28, 6 and 12 weeks from the first CD5CAR-CBNK cell infusion and from study inclusion.
Assess the efficacy of CD5CAR-CBNK cells.	Overall response rate (ORR)	at day 28, 6 and 12 weeks from the CD5CAR-CBNK cell infusion and inclusion of the patient.
Assess the efficacy of CD5CAR-CBNK cells.	Time to response calculated from the day of infusion to the date when the patient first meets the criteria for partial or complete response.	During the first year after first administration
Assess the efficacy of CD5CAR-CBNK cells.	Duration of response: defined as the time between first response and loss of response.	During the first year after first administration
Assess the efficacy of CD5CAR-CBNK cells.	Event-free survival (EFS) calculated from CD5CAR-CBNK cell infusion and study inclusion to the date of first occurrence of any of the following events: (i) Fungal disease progression (radiological or clinical). (ii) Loss of response or fungal recurrence (iii) Severe therapy-related toxicity. (iv) Death for any cause.	During the first year after first administration
To quantify persistence and kinetics of allogeneic CD5CAR-CBNK cells in blood after administration.	Number of circulating CD5CAR-CBNK cells in peripheral blood	During the first year after first administration
To quantify persistence and kinetics of allogeneic CD5CAR-CBNK cells in blood after administration.	Changes in serum pro-inflammatory and anti-inflammatory cytokines	During the first year after first administration
To quantify persistence and kinetics of allogeneic CD5CAR-CBNK cells in blood after administration.	CD5 expression	During the first year after first administration
To quantify persistence and kinetics of allogeneic CD5CAR-CBNK cells in blood after administration.	Percentage of transduction, T-cell, NK-cell and B-cell subsets, and exhaustion and senescence population	During the first year after first administration

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses
• Other Study ID Numbers: 2025-524638-24-00

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: No
• Studies a U.S. FDA-regulated device product: No