Safety and Efficacy of Fourth-Generation CAR-T in the Treatment of Hematologic Malignancies

NCT ID: NCT06758713

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-15
• Study Completion Date: 2028-12-31

Brief Summary

This is a single center, open-label, dose-escalation/expansion clinical study to evaluate the safety and effectiveness of Fourth-Generation CAR-T, and determine the recommended dose of the CAR T-cells for patients with Multiple Myeloma，B-cell lymphoma and other hematologic malignancies.

Detailed Description

This is a single center, open-label, dose-escalation/expansion clinical study to evaluate the safety and efficacy of Fourth-Generation CAR-T in the Treatment of Multiple Myeloma，B-cell lymphoma and other hematologic malignancies.. -Prior to Fourth-Generation CAR-T cells infusion, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the investigators will observe the characteristics of dose limited toxicity (DLT), and determine the maximum tolerable agent MTD and RP2D were confirmed. To provide basis for the dosage and treatment plan of cell products in follow-up clinical trials. Meanwhile, subjects will be followed for side effects and effect of the CAR-T.

Conditions

Multiple Myeloma; B-cell Lymphoma; Hematological Malignancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1:Low dose group

Infusion of CAR T-cells by single dose of 0.5×10\^6 CAR-T cells/kg

Group Type: EXPERIMENTAL

CAR-T

Intervention Type: BIOLOGICAL

CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting human B cell maturation antigen (BCMA) ,CD19 or CD-7 etc. target molecules of other hematologic malignancies.

Phase 1: Medium dose group

Infusion of CAR T-cells by single dose of 1.5×10\^6 CAR-T cells/kg

Group Type: EXPERIMENTAL

CAR-T

Intervention Type: BIOLOGICAL

CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting human B cell maturation antigen (BCMA) ,CD19 or CD-7 etc. target molecules of other hematologic malignancies.

Phase 1: High dose group

Infusion of CAR T-cells by single dose of 5.0×10\^6 CAR-T cells/kg

Group Type: EXPERIMENTAL

CAR-T

Intervention Type: BIOLOGICAL

CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting human B cell maturation antigen (BCMA) ,CD19 or CD-7 etc. target molecules of other hematologic malignancies.

Phase 2a: RP2D

After all subjects in the Phase 1 dose-escalation study completed DLT observation, RP2D was determined based on the analysis results for the phase 2a expansion study.

Group Type: EXPERIMENTAL

CAR-T

Intervention Type: BIOLOGICAL

CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting human B cell maturation antigen (BCMA) ,CD19 or CD-7 etc. target molecules of other hematologic malignancies.

Interventions

CAR-T

CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting human B cell maturation antigen (BCMA) ,CD19 or CD-7 etc. target molecules of other hematologic malignancies.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Subjects must meet all of the following criteria to be enrolled:

1. Voluntarily participate in this clinical study and sign the informed consent form; 2. 18 to 75 years old (including cut-off value), Male and female;; 3. Expected survival of at least 3 months; 4.1 CD19-positive B lymphocyte-derived hematologic malignancies; 4.2 Multiple myeloma patients; 4.3 Non-B cell-derived hematologic malignancies patients with CD7 or other target molecules; 5. The clinical trial values during the screening period meet the following criteria:

1. White blood cell count ≥ 3.0 × 10e9/L; Absolute neutrophil ≥ 1.0 × 10e9/L; Lymphocyte count ≥ 0.5 × 10e9/L. (The growth factor support is allowed, but growth factor must not have been received within 7 days prior to laboratory testing);

2. Platelet count ≥ 50 × 10e9/L (No blood transfusion support within 7 days prior to laboratory tests.); Note: Patients with leukemia, multiple myeloma, and lymphoma are not subject to the above blood picture requirements;

3. Biochemical indicators Serum total bilirubin (TBIL) ≤ 2.5 ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN, or 5 ULN if liver dysfunction is primarily due to tumor invasion); 6. Cardiac function: Subjects must have good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥ 55%; 7. Lung condition: Subjects are not serious infections such as severe pneumonia; 8. ECOG activity status score: 0-2 points; 9. Female subjects must use effective contraception (such as oral prescription contraceptives, injectable contraceptives, intrauterine devices, double blockade, contraceptive patches, male partner sterilization) throughout the study period; Must have a negative serum or urine pregnancy test result at screening and throughout the study.

Exclusion Criteria

Any one of the following conditions cannot be selected as a subject:

1. Having received CAR-T therapy targeting the same molecule;

2. Having received other immunotargeted therapy targeting the same molecules;

3. Pregnant or lactating women;

4. Subjects who have previously suffered from other malignancies, with the following exceptions:

1. Having received curative therapy, and no known active disease in the ≥ 3 years prior to the enrollment;

2. Non melanoma skin cancer subjects who have completed sufficient treatment and no evidence of thecurrent disease;

5. Subjects with a severe mental disorder;

6. Subjects with active autoimmune disease requiring immunotherapy;

7. Having received allogeneic hematopoietic stem cell transplantation;

8. Subjects with significant cardiovascular diseasesa.uncontrolled or symptomatic arrhythmias, congestive heart failure, or any heart disease with cardiac function grade 3 or grade 4 (according to the functional classification method of the New York Heart Association NYHA); b. Myocardial infarction or coronary artery bypass grafting within 6 months prior to screening); c. Clinically significant history of ventricular arrhythmia or unexplained syncope (non vaso-vagal or not due to dehydration);

9. Subjects with active infectious disease including positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood Hepatitis B virus(HBV) DNA titer is ≥500IU/mL, hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive, human immunodeficiency virus(HIV) antibody positive, syphilis primary screening antibody positive, active pulmonary tuberculosis; or with any significant infection requiring high-grade antibiotics Event;

10. Subjects with dysfunction of important organssuch as organ function in the following abnormalities:

1. Serum AST or ALT > 2.5×ULN, or > 5ULN if liver function is predominantly due to tumor invasion; TBIL > 2.5 × ULN, unless the subject is Gilbert's syndrome;

2. Serum creatinine>2.5mg/dl;

3. Partial prothrombin time or activated partial thromboplastin time or international normalized ratio > 1.5×ULN in the absence of anticoagulant therapy;

11. Participation in other clinical studies or prior treatment with any gene therapy product in the past three months;

12. Subjects with uncontrolled diabetes mellitus (glycosylated hemoglobin HbAlc >8% at screening);13. Highly allergic constitution or history of severe allergies, and having contraindications to cyclophosphamide or fludarabine;

14. Feasibility assessment screening demonstrated <10% transfection of targeted lymphocytes or underamplification under CD3 / CD28 costimulation (<5-fold); 15. Subjects who are considered unsuitable to participate in this trial by the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Third Affiliated Hospital of Southern Medical University

OTHER_GOV

Sponsor Role: lead

Responsible Party

Yan Yi

MD.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yan Yi, MD.

Role: STUDY_DIRECTOR

Locations

The Third Affiliated Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yan Yi, MD.

Role: CONTACT

yiyan@smu.edu.cn

+86 13617493781

Facility Contacts

Yan Yi, MD.

Role: primary

yiyan@smu.edu.cn

+86 13617493781

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Other Identifiers

2024-Lunli-020

Identifier Type: OTHER

Identifier Source: secondary_id

2024-Lunli-020

Identifier Type: -

Identifier Source: org_study_id