Study of the Infusion of ARI-0001 Cells in Patients With CD19 + Acute Lymphoid Leukemia Resistant or Refractory to Therapy

Phase 2

Not yet recruiting

Conditions: Acute lymphoid leukemia

Registration Number: 2024-513601-31-00

Lead Sponsor: Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Brief Summary: To assess the efficacy (in terms of response rate and duration) of the infusion of ARI-0001 cells (Adult differentiated autologous T-cells from peripheral blood, expanded and transducted with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity [A3B1] conjugated to the 4-aBB and CD3z co-stimulatory regions) in patients with resistant or refractory CD19+ acute lymphoid leukemia

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

Diagnoses of CD19+ acute lymphoid leukemia, with a life expectancy of less than 2 years that meet the following conditions: Relapsed/refractory not candidate for transplantation (due to associated diseases or absence of donor) or in allogenic post-transplant relapse.

Measurable disease understood as the presence of measurable residual disease by flow cytometry in bone marrow or peripheral blood

Age less than 70 years (from 18 to 70)

ECOG functional status from 0 to 2

Life expectancy of at least 3 months.

Adequate venous access to perform a lymphapheresis. Absence of contraindications for it

Signature of informed consent

Exclusion Criteria

Treatment with any experimental or non-marketed substance within four weeks prior to recruitment, or actively participating in another therapeutic trial

Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBc antibodies it will be necessary to perform a DNA test of the hepatitis B virus, and if the result is positive the patient will be excluded

Positive serology for hepatitis C, defined as a positive test for anti-VHC antibodies confirmed by RIBA

Concurrent uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric diseases that in the opinion of the investigator are potential risk factors to the patient

Severe organ involvement, defined as cardiac ejection fraction <40%; DLCO <40%; calculated glomerular filtrate <30 ml/min; or bilirubin > 3 times the upper limit of normality (unless Gilbert syndrome)

Pregnant or lactating women. Woman of childbearing potential should have a negative pregnancy test in the screening phase.

Women of childbearing potential, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective contraceptive methods* from the start of the study to the completion of the study.

Men who cannot or do not wish to use highly effective contraceptive methods* from the beginning of the study until the end of the study

Previous treatment with CART therapy (commercial or experimental)

Diagnosis of another neoplasm, past or present. Patients may be included in complete remission for more than 3 years, or have a history of non-melanoma skin cancer or in-situ carcinoma resected completely.

Relief of central nervous system (CNS-3) at the time of inclusion. Inclusion will be permitted in patients with a lower grade (CNS-2) or CNS-3 who have responded to intrathecal chemotherapy

Isolated extramedullary involvement (i.e. in the absence of minimal residual disease in peripheral blood, bone marrow, or cerebrospinal fluid)

Early relapse after transplantation (less than 3 months for mononuclear cell apheresis, less than 6 months for infusion of ARI-0001)

Active immunosuppressive treatment for graft-versus-host disease and other diseases. The use of corticosteroids to control leukaemia at the time of inclusion should be limited as much as possible and should be discontinued prior to infusion of ARI-0001 cells.

Active infection requiring systemic medical treatment such as chronic kidney infection, chronic lung infection or tuberculosis.

HIV infection

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Response rate with measurable residual disease negative by multiparametric flow cytometry 28 days after infusion of ARI-0001 cells.		Response rate with measurable residual disease negative by multiparametric flow cytometry 28 days after infusion of ARI-0001 cells.

Secondary Outcome Measures

Name	Time	Method
Duration of response		Duration of response
Best response during the first 3 months of follow-up after administration of the first fractioned dose of ARI-0001		Best response during the first 3 months of follow-up after administration of the first fractioned dose of ARI-0001
Progression-free survival at 6 months and 1 year of the infusion and after the signature of informed consent.		Progression-free survival at 6 months and 1 year of the infusion and after the signature of informed consent.
Overall Survival (OS) at 1 year of the infusion and after the informed consent form signature		Overall Survival (OS) at 1 year of the infusion and after the informed consent form signature
Assessment of ARI-0001 cell toxicity considering special interest in the following adverse events: CRS (cytokine release syndrome), encephalopathy associated with CARs (ICANS) and cerebral edema. Mortality related to study procedures and adverse events grade 3-4 will be evaluated at month 3 and year 1. Intensity will be assessed using CTCAE version 5.0 scale. To evaluate CRS and neurotoxicity ASTCT criteria will be used.		Assessment of ARI-0001 cell toxicity considering special interest in the following adverse events: CRS (cytokine release syndrome), encephalopathy associated with CARs (ICANS) and cerebral edema. Mortality related to study procedures and adverse events grade 3-4 will be evaluated at month 3 and year 1. Intensity will be assessed using CTCAE version 5.0 scale. To evaluate CRS and neurotoxicity ASTCT criteria will be used.
In vivo survival of ARI-0001 cells in peripheral blood, bone narrow and cerebrospinal fluid, to be determined by flow cytometry and quantitative transgene PCR with monthly frequency in the first 6 months and thereafter quarterly up to 2 years of infusion		In vivo survival of ARI-0001 cells in peripheral blood, bone narrow and cerebrospinal fluid, to be determined by flow cytometry and quantitative transgene PCR with monthly frequency in the first 6 months and thereafter quarterly up to 2 years of infusion

Trial Locations

Locations (9): Hospital De La Santa Creu I Sant Pau
🇪🇸
Barcelona, Spain
Hospital Germans Trias I Pujol
🇪🇸
Badalona, Spain
University Clinical Hospital Virgen De La Arrixaca
🇪🇸
Murcia, Spain
University Hospital Virgen Del Rocio S.L.
🇪🇸
Sevilla, Spain
Hospital Clinic De Barcelona
🇪🇸
Barcelona, Spain
Hospital Universitario 12 De Octubre
🇪🇸
Madrid, Spain
Hospital Universitario De Salamanca
🇪🇸
Salamanca, Spain
Clinica Universidad De Navarra
🇪🇸
Pamplona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Javier Briones
Site contact
+34935565649
jbriones@santpau.cat