Allogeneic CARCIK-CD19 in adults/pediatric B-cell Non Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Tettamanti

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

29 Jan 2024 → ongoing

Decision date (initial)

2023-11-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fondazione Tettamanti

External identifiers

EU CT number

2023-505511-20-00

ClinicalTrials.gov

NCT05869279

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy, Pharmacodynamic

Phase I
To identify the recommended Phase 2 dose (RP2D) of allogeneic, HLA haploidentical familial CARCIK-CD19 cells in B-cell NHL

Phase II
To evaluate the efficacy of CARCIK-CD19 infusion in terms of overall response rate

Secondary objectives 1

1. 1.To further characterize the safety profile of CARCIK-CD19 therapy 2.To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of CARCIK-CD19 cells in peripheral blood and other tissues, if available 3. To describe the persistence of lymphoid chimerism (peripheral blood) after CARCIK-CD19 infusion 4. To describe the levels of B, T and NK cells (peripheral blood) prior to and following CARCIK-CD19 infusion 5. To evaluate the efficacy in terms of best overall response rate in infused patients 6. To evaluate the duration of response (DOR) 7. To evaluate the disease-free survival (DFS) 8. To evaluate progression-free survival (PFS) 9. To evaluate overall survival (OS)

Conditions and MedDRA coding

B-Non Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Able and willing to provide written informed consent and to comply with the study protocol according to ICH and local regulations. 2. Ineligibility to commercially available CAR-T cells 3. Age limits: children (1-17 years old) and adults (≥18 years old) 4. Availability of an at least haploidentical (i.e. 4/8 HLA matched by allele typing) familial donor willing to and eligible for blood donation 5. Histologically-confirmed mature B-cell neoplasia (NHL), according to according to WHO 2021 classification: • Eligible histologies include: indolent [follicular lymphoma (FL) or marginal zone lymphoma (MZL) nodal; extra-nodal; or splenic] or aggressive [diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBL), high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), mantle cell lymphoma (MCL), including transformed B-cell NHL], CLL or lymphocytic lymphoma (LL). high-grade B cell lymphoma (HGBCL) NOS. Additional histologies including Burkitt lymphoma and Richter syndrome will be considered upon review with Sponsor. 6. Relapsed after or refractory to at least two prior lines of treatment, and no available treatment options that are expected to prolong survival (e.g. chemotherapy or high-dose chemotherapy/stem cell transplantation, commercially available CART cell therapy or other standard treatment) or patients refusing such treatments 7. At least one measurable target lesion, measurable as defined by Lugano 2014 classification (nodal: > 1.5 cm longest transverse diameter; extra-nodal: > 1 cm longest transverse diameter) by computerized tomography (CT) scan or presence of assessable disease (i.e. bone marrow or spleen) 8. Eastern Cooperative Oncology Group (ECOG) performance status equal to 2 or less for subject ≥ 16 years of age, ore Lansky >50 for subjects < 16 years of age

Exclusion criteria 1

1. Patients with clinically significant active viral, bacterial or fungal infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 2 weeks prior to CARCIK-CD19 infusion. 2) Patients with an active infection with Hepatitis B. However, patients with a controlled (treated) hepatitis will be allowed if the all the following criteria are met: • Anti-viral therapy for hepatitis B virus (HBV) must be given for at least 1 month prior to time of informed consent; • HBV viral load must be <2000 IU/mL (104 copies/mL) prior to time of informed consent; and • those on active HBV therapy with viral load <2000 IU/mL (104 copies/mL) should stay on the same anti-viral therapy throughout study treatment 3) Patients with an active hepatitis C virus (HCV) infection. However, patients with successfully treated chronic HCV infection will be allowed if they show a sustained virologic response at 12 weeks (SVR12) or 24 weeks (SVR24), and if there is a 4-week period between achieving sustained viral response (SVR12 or SVR24) and time of informed consent. 4) Patients with a positive serologic test or a positive molecular PCR test for human immunodeficiency virus (HIV) are eligible if asymptomatic, well controlled by the HAART therapy and no medically significant active infection is present 5) Rapidly progressive disease that in the estimation of the investigator and sponsor could affect compliance with the protocol or interpretation of results 6) Active CNS lymphoma

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase I • DLT as per investigator assessment during the first 28 days after CARCIK-CD19 infusion [population: patients treated with CARCIK-CD19] Phase II • Investigator-assessed overall response rate (complete + partial remission) at month 3 after CARCIK-CD19 infusion according to 2014 Lugano criteria (iwCLL 2018 criteria for CLL). [population: patients treated with CARCIK-CD19]

Secondary endpoints 1

1. • Incidence of Adverse event (AE) and laboratory abnormalities continuously assessed throughout the study and reported at each scheduled visit. Description and grading of all adverse events will be based on the NCI –CTCAE and MedDRA code (current version) • Persistence and kinetics of CARCIK-CD19 cells in target tissues (blood, bone marrow, and other tissues if available)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Tettamanti

Sponsor organisation

Fondazione Tettamanti

Address

Via Giovanni Battista Pergolesi 33

City

Monza

Postcode

20900

Country

Italy

Scientific contact point

Organisation

Fondazione Tettamanti

Contact name

secretariat of the scientific directorate

Public contact point

Organisation

Fondazione Tettamanti

Contact name

secretariat of the scientific directorate

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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