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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 May 2024 → ongoing

Decision date (initial)

2024-05-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III

External identifiers

EU CT number

2024-513601-31-00

EudraCT number

2019-003038-17

ClinicalTrials.gov

NCT04778579

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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

Secondary objectives 3

1. Assess adverse events occurring at 3 months and per year
2. To assess overall survival after infusion of ARI-0001
3. To evaluate the duration of ARI-0001 cells in peripheral blood, bone marrow and CSF after administration

Conditions and MedDRA coding

Acute lymphoid leukemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003264-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Measurable disease understood as the presence of measurable residual disease by flow cytometry in bone marrow or peripheral blood
3. Age less than 70 years (from 18 to 70)
4. ECOG functional status from 0 to 2
5. Life expectancy of at least 3 months.
6. Adequate venous access to perform a lymphapheresis. Absence of contraindications for it
7. Signature of informed consent

Exclusion criteria 16

1. Treatment with any experimental or non-marketed substance within four weeks prior to recruitment, or actively participating in another therapeutic trial
2. Previous treatment with CART therapy (commercial or experimental)
3. 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.
4. 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
5. Isolated extramedullary involvement (i.e. in the absence of minimal residual disease in peripheral blood, bone marrow, or cerebrospinal fluid)
6. Early relapse after transplantation (less than 3 months for mononuclear cell apheresis, less than 6 months for infusion of ARI-0001)
7. 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.
8. Active infection requiring systemic medical treatment such as chronic kidney infection, chronic lung infection or tuberculosis.
9. HIV infection
10. 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
11. Positive serology for hepatitis C, defined as a positive test for anti-VHC antibodies confirmed by RIBA
12. 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
13. 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)
14. Pregnant or lactating women. Woman of childbearing potential should have a negative pregnancy test in the screening phase.
15. 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.
16. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 6

1. Duration of response
2. Best response during the first 3 months of follow-up after administration of the first fractioned dose of ARI-0001
3. Progression-free survival at 6 months and 1 year of the infusion and after the signature of informed consent.
4. Overall Survival (OS) at 1 year of the infusion and after the informed consent form signature
5. 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.
6. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

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

Contact name

Jordi Esteve Reyner

Public contact point

Organisation

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

Contact name

Jordi Esteve Reyner

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications