Intravenous Autologous CD19 CAR-T Cells for R/ R MM, B-ALL, and B-Cell Lymphoma

Official title

An Early Exploratory Clinical Study of Enhanced Autologous CAR-T Cell Injection (ECAR01) Targeting CD19 and BCMA in Patients With Relapsed or Refractory Multiple Myeloma, Acute B-Cell Leukemia, and B-Cell Lymphoma

Overview

This is an open label, single-site, dose-escalation study in up to 18 participants with Relapsed or Refractory Multiple Myeloma, Acute B-Cell Leukemia, and B-Cell Lymphoma. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART

Interventions

• Drug Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis
  A single intravenous infusion of anti-BCMA and CD19 CART cells (dose-escalating infusion of 1.0-5.0 x10\^5 CART cells/kg）.

Primary outcome measures

• 1. Adverse events [Time frame: up to 2 years]

Secondary outcome measures (4)

• 2.The persistence, accumulation, and migration of CART cells [Time frame: up to 2 years]
• Progression free survival (PFS) [Time frame: up to 2 years]
• Overall survival (OS) [Time frame: up to 2 years]
• Objective Response Rate (ORR) [Time frame: up to 2 years]

Eligibility criteria

Inclusion criteria

• The patient or his/her guardian is fully informed and agrees to participate in this clinical study and signs the informed consent form;
• At the time of signing the informed consent form, be over 3 years of age, regardless of gender;
• Patients with a confirmed diagnosis of acute B-cell leukemia/B-cell lymphoma/multiple myeloma who meet one of the following criteria:

• 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.
• 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.
• Multiple Myeloma: Patients with confirmed diagnosis of multiple myeloma and patients with relapsed or refractory multiple myeloma according to IMWG 2016 diagnostic criteria.
• 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;
• For patients with B-ALL, the proportion of bone marrow primitive and naïve lymphocytes in the screening period ≥5%;
• 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;
• 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;
• ECOG score: 0\~2 points;
• As judged by the investigator, the patient has an expected survival of more than 3 months;
• 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

• 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;
• patients with B-ALL with confirmed diagnosis of isolated extramedullary recurrence;
• presence of malignancies other than acute B-cell leukemia/B-cell lymphoma;
• 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;
• Vaccination, B-cell targeted therapy within 4 weeks prior to screening;
• Patient has systemic autoimmune disease or immunodeficiency;
• Grade 2\~4 acute graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within 4 weeks prior to screening;
• Patients with relatively serious heart disease, such as angina, myocardial infarction, heart failure and arrhythmia;
• History of severe allergy to drugs used in clinical studies or raw and excipient materials of experimental drugs, such as cyclophosphamide, fludarabine, DMSO, etc.;
• Patient has active hepatitis B, or positive HCV antibody, or HIV antibody, or syphilis;
• Presence of active infection requiring intravenous antibiotics or hospitalization;
• Pregnant or lactating women;
• 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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of University of Science and Technology of China — Hefei

Identifiers

NCT: NCT06961669 · SWKCAR-T2024062401

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗