Intravenous Autologous CD19 CAR-T Cells for R/ R B-ALL and B-cell Lymphoma (ECAR01)

University of Science and Technology of China (USTC)

Status: Enrolling

Conditions: Lymphoblastic Leukemia

Treatments: Drug: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis

Study type: Interventional

Funder types: Other

Identifiers

NCT06961669

SWKCAR-T2024062401

Details and patient eligibility

About

This is an open label, single-site, dose-escalation study in up to 18 participants with Relapsed or refractory B-lymphoblastic leukemia and B-cell lymphoma. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART

Enrollment: 18 estimated patients

Sex: All

Ages: 3+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. The patient or his/her guardian is fully informed and agrees to participate in this clinical study and signs the informed consent form;

2. At the time of signing the informed consent form, be over 3 years of age, regardless of gender;

3. Patients with confirmed diagnosis of acute B-cell leukemia/B-cell lymphoma:

   a. B diffuse large B-cell lymphoma (DLBCL), germinal center, or activated B-cell type; Primary cutaneous DLBCL; Primary mediastinal (thymic) large B-cell lymphoma; ALK anaplastic large B-cell lymphoma; High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (i.e., "double or triple hit"); High-grade B-cell lymphoma; T-cell-rich B-cell lymphoma; transformed follicular lymphoma; or any aggressive B-cell lymphoma caused by indolent lymphoma; follicular lymphoma; mantle cell lymphoma; Patients with large cell transformation (Richter's Transformation) with CLL who have not achieved remission or have progressed after achieving remission after at least 1 prior line of therapy.

4. Patients diagnosed with acute B-cell leukemia: Patients who have achieved relapse after achieving remission after prior chemotherapy; or patients who have failed to achieve remission (<5% bone marrow blasts or persistent extramedullary or central nervous system disease) after 2 prior cycles of induction chemotherapy, or who still maintain MRD.

5. For patients with B-cell lymphoma, according to the recommendations for initial evaluation, staging, and response evaluation of Hodgkin and non-Hodgkin lymphoma (2014 edition), at least one measurable lesion in the baseline period, i.e., lymph node lesions with a length diameter of > 15 mm, or an extranodal lesion with a length diameter of > 10 mm according to PETCT or CT imaging;

6. For patients with B-ALL, the proportion of bone marrow primitive and naïve lymphocytes in the screening period ≥5%;

7. CD19 expression of tumor cells confirmed by flow cytometry or immunohistochemistry: the proportion of CD19 cells detected by peripheral blood flow cytometry in patients with B-ALL was ≥30%, and the proportion of CD19 cells in patients with B-cell lymphoma was positive by immunohistochemistry;

8. Adequate function of vital organs: liver function satisfies ALT≤3×ULN, AST≤3×ULN; serum creatinine≤140μmol/L; Total bilirubin ≤ 2× ULN, and total bilirubin ≤ 3.0× ULN for patients with Gilbert syndrome; Haemodynamically stable and left ventricular ejection fraction (LVEF) ≥45% as determined by echocardiography or multichannel radionuclide angiography (MUGA); No active pulmonary infection, transcutaneous arterial oxygen saturation ≥92% in non-oxygen-based state;

9. ECOG score: 0~2 points;

10. As judged by the investigator, the patient has an expected survival of more than 3 months;

11. Subjects of childbearing potential agree to use a reliable and effective method of contraception (excluding contraception during the safe period) for 2 years from the time of signing the informed consent form until receiving ECAR01 cell infusion.

Exclusion criteria

1. Episodes of central nervous system disease or presence of pathological changes within 6 months prior to screening, including but not limited to: stroke, stroke, aneurysm, epilepsy, convulsions, aphasia, severe head injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or mental disorder;
2. patients with B-ALL with confirmed diagnosis of isolated extramedullary recurrence;
3. presence of malignancies other than acute B-cell leukemia/B-cell lymphoma;
4. Received the following anti-tumor therapies before cell collection: chemotherapy, targeted therapy, and other drug therapy within 14 days or at least 5 half-lives; Radiotherapy within 14 days;
5. Vaccination, B-cell targeted therapy within 4 weeks prior to screening;
6. Patient has systemic autoimmune disease or immunodeficiency;
7. Grade 2~4 acute graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within 4 weeks prior to screening;
8. Patients with relatively serious heart disease, such as angina, myocardial infarction, heart failure and arrhythmia;
9. History of severe allergy to drugs used in clinical studies or raw and excipient materials of experimental drugs, such as cyclophosphamide, fludarabine, DMSO, etc.;
10. Patient has active hepatitis B, or positive HCV antibody, or HIV antibody, or syphilis;
11. Presence of active infection requiring intravenous antibiotics or hospitalization;
12. Pregnant or lactating women;
13. Other investigators believe that the subject is not suitable to participate in this clinical study because it will affect the safety and efficacy judgment of the subject, or for other reasons;

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Experimental: Anti-BCMA and CD19 CART

Experimental group

Description:

Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of Anti-BCMA and CD19 CART will be infused on day 0.

Treatment:

Drug: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis