Therapeutic strategy driven by residual disease for CARCIK-CD19 in patients with relapsed/refractory B cell precursor Acute Lymphoblastic 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

22 Sep 2021 → 13 May 2025

Decision date (initial)

2024-12-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-519394-19-00

EudraCT number

2020-005025-85

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To confirm the high overall response rate at day 28 after the first CARCIK-CD19 infusion and to improve the duration of response of patients treated with CARCIK -CD19 cells.

Secondary objectives 1

1. Overall survival (OS) and Safety of the second administration of allogeneic CARCIK-CD19 cells

Conditions and MedDRA coding

B cell precursor Acute Lymphoblastic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Children (1-17) and adults (18-75 years old);
2. Relapsed or refractory adult and pediatric BCP-ALL as defined for the presence of bone marrow with ≥ 5% lymphoblasts by morphologic assessment, or if <5%, with at least 1% of molecular disease at PCR;
3. Evidence of CD19 tumor expression in bone marrow and/or peripheral blood by flow cytometry;
4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening, or if <5%, with at least 1% of molecular disease at PCR;
5. No evidence of overall aGVHD > Grade I or chronic GVHD (cGVHD) greater than mild at time of enrollment and in the previous 30 days;
6. No longer taking immunosuppressive agents for at least 30 days prior to infusion;
7. No evidence of concomitant life-threatening infectious disease;
8. Life expectancy > 60 days;
9. Lansky/Karnofsky scores > 60;
10. Absence of severe renal disease (creatinine > x 3 normal for age);
11. Absence of severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500);
12. Patient/guardian able to give informed consent.

Exclusion criteria 11

1. GVHD Grades II-IV for patients who had previously been transplanted;
2. Any cell therapy in the last 30 days;
3. Patient with concomitant life-threatening infectious disease;
4. Lansky/Karnofsky score <60;
5. Patients with hepatic or renal disease as specific above;
6. Pregnant or breast feeding females;
7. Rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
8. Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met;
9. HIV/HBV/HCV Infection: Seropositive for HIV antibody. Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HBsAG);
10. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris and cardiac arrhythmia;
11. Active Central Nervous System (CNS) involvement by malignancy, defined as CNS-3 per National Comprehensive Cancer Network (NCCN) guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. ORR at 28 days after the first CARCIK-CD19 administration
2. DOR from day 70 for patients who achieved and maintained remission after the first or the second CARCIK-CD19 administration

Secondary endpoints 4

1. Overall survival (i. e. time from infusion to death)
2. Safety of the second administration of allogeneic CARCIK-CD19 cells
3. Safety of autologous CARCIK-CD19 cells
4. Safety of cordblood CARCIK-CD19 cells.

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

Giuseppe Dastoli

Public contact point

Organisation

Fondazione Tettamanti

Contact name

Stefania Monterisi

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

Results and documents

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

Documents 6 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