This Clinical Trial is a Single-arm, Non-randomized Pilot Trial to Determine the Safety of Administering Autologous Anti-C19 Cells (ARI-0001) and the Feasibility of Local CAR-T Cell Production in Patients Over 18 Years of Age With Relapsed/Refractory (R/R) CD19+ Hematologic Malignancies, Including R

ConditionsAdult B-cell Acute Lymphoblastic Leukemia Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)Diffuse Large B-Cell Lymphoma (DLBCL)Chronic Lymphocytic Leukemia

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18-80

SponsorGUSTAVO SALGUERO

About this trial

This is a hybrid type two study, with two simultaneous development phases. Phase A involves developing a public-private partnership to create the conditions for implementing CAR-T cell therapies in Colombia. Phase B will be a single-arm, non-randomized pilot clinical trial in patients over 18 years of age with recurrent/refractory (R/R) CD19+ hematopoietic lymphoid neoplasms, including R/R non-Hodgkin lymphoma (NHL), R/R B-cell acute lymphoblastic leukemia (B-ALL), and R/R mantle cell lymphoma; and R/R chronic lymphocytic leukemia (CLL) (including CLL with Richter transformation). This trial aims to determine the safety of administering autologous anti-C19 cells (ARI-0001) and the feasibility of local CAR-T cell production.

Phase A of implementation aims to gather information on the domains of the multilevel model, including organizational context, suppliers, infrastructure, and institutional capacities, to identify barriers and facilitators in the implementation of CAR-T cell therapy in Colombia. National consensus will also be developed in the scientific, clinical, administrative, and regulatory spheres.

Phase B will involve a pilot clinical trial in patients with relapsed/refractory CD19-positive hematopoietic lymphoid neoplasms. The production of ARI-0001 cells consists of the genetic modification of autologous T cells through lentiviral transduction of a chimeric antigen receptor (CAR) targeting the CD19 surface antigen. The process is carried out in the CliniMACS Prodigy® closed transduction system, which for this study will be located at and operated by staff from the District Institute of Science, Biotechnology, and Innovation in Health (IDCBIS). This pilot clinical trial will use an open-label, single-arm, staggered enrollment design with a safety observation period. The patient will receive the cell product infusion following administration of a lymphodepletion regimen at the National Cancer Institute (NCI). The patient will remain hospitalized for 14 days after the CAR-T cell infusion ARI-001 for medical monitoring, with subsequent outpatient follow-up until 12 months post-infusion.

Subsequently, the patient will be offered a new informed consent process to participate in outpatient follow-up for up to 15 years.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants (Men and Women) ≥ 18 and ≥ 80 years of age.

Participants capable of understanding and voluntarily signing the informed consent forms (prescreening and study forms) prior to any study-related evaluation or procedure, and able to adhere to the study visit schedule and other protocol requirements.

CD19+ hematologic malignancy with a histologically documented diagnosis.

Inclusion criteria according to the type of CD19+ hematologic malignancy measurable by the 2014 Lugano criteria (NHL) or IWCLL criteria (CLL) or EWALL criteria (ALL).

Disqualifiers

Failure to comply with the washout periods.

Autologous or allogeneic stem cell transplantation or CAR-T cell therapy within 6 weeks prior to CAR-T cell infusion.

Subjects with an active infection requiring systemic treatment. This definition excludes participants with Hepatitis B (known positive hepatitis B surface antigen [HBsAg] result), latent Tuberculosis, Hepatitis C, or HIV seropositivity.

History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) requiring immunosuppressive medication within the past 6 months.

Trial design

Design model

Single group

Treatments tested in this trial

ARI-0001 T cells with anti-CD19 chimeric antigen receptor (CAR-T)
Biological/Vaccine
Pilot clinical trial ARI-0001 T cells with anti-CD19 chimeric antigen receptor (CAR-T) treatment of recurrent/refractory CD19+ hematolymphoid neoplasms.

Treatment groups

12 Participants

are divided into 1 treatment group

Group A: Single-arm, non-randomized pilot clinical trial in patients aged between 18 and 80 yearsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1. Clinical Safety Outcome (Pilot Cohort)

Proportion of patients experiencing grade ≥3 treatment-related adverse events, including cytokine release syndrome (CRS), CAR-T cell-associated neurotoxicity (ICANS), and prolonged cytopenias beyond 30 days post-infusion (ICAHT).

Time frame

This outcome will be assessed 30 days post-infusion.

2. Clinical Safety Outcome (Pilot Cohort)

Proportion of patients developing infections within the first 12 months after CAR-T cell infusion.

Time frame

12 months after CAR-T cell infusion.

3. Clinical Safety Outcome (Pilot Cohort)

Early mortality, defined as death occurring within the first 30 days post-infusion.

Time frame

30 days post-infusion.

Secondary outcomes

Overall response rate (ORR)

1\. Overall response rate (ORR) at 28 and 100 days post-infusion, according to specific diagnostic criteria for each type of CD19+ neoplasm.

Time frame

at 28 and 100 days post - infusion

Disease-free survival (DFS)

at 12 and 24 months post-infusion, defined as the time from infusion to progression or death, stratified by type of CD19+ neoplasm.

Time frame

at 12 and 24 months post - infusion

Overall survival (OS)

at 12 and 24 months post-infusion, defined as the time from infusion to death.

Time frame

at 12 and 24 months post-infusion

Other outcomes

Exploratory Outcomes: Persistence of ARI-0001 CAR-T cells in peripheral blood

Persistence of ARI-0001 CAR-T cells in peripheral blood by flow cytometry and quantitative PCR (qPCR) at 28, 100, 180, and 360 days post-infusion.

Time frame

at 28, 100, 180, and 360 days post-infusion.

Exploratory Outcomes: Direct and indirect costs

Direct and indirect costs of manufacturing, lymphodepletion, infusion, and management of complications related to CAR-T therapy (ARI-0001).

Time frame

Through study completion, an average of 1 year

Exploratory Outcomes: Immunological profile and inflammatory markers

Immunological profile and inflammatory markers 1. Analysis of T cell subpopulations, including CD4+ T cells, CD8+ T cells, regulatory T cells, and memory T cells, on days +28, +100, and +360. 2. Percentage of B lymphocyte subpopulations (CD19+, CD27+, IgD+, plasmablasts) on days +28, +100, and +360. 3. Serum levels of proinflammatory cytokines (IL-6, IL-1β, IFN-γ, TNF-α), LDH, ferritin, and D0 infusion +28 and +100 post-infusion.

Time frame

on days +28, +100, and +360.

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

GUSTAVO SALGUERO

Lead sponsor

Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud - IDCBIS

Sponsor institution

Instituto Nacional de Cancerologia, Columbia

Collaborator

Source ClinicalTrials.gov

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