A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Unknown; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: C-CAR088

Study type: Interventional

Funder types: Other

Identifiers

NCT04322292

QT-2019007-EC-2

Details and patient eligibility

About

This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR088 in relapsed or refractory multiple myeloma patient.

Full description

The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18-75 years old, male or female;

2. The patient volunteered to participate in the study, and he or his legal guardian signed the Informed Consent;

3. Meet the internationally accepted Criteria for the diagnosis of multiple myeloma (IMWG diagnostic criteria 2014);

4. Patients with a clear diagnosis of relapsed or refractory multiple myeloma who have received at least 3 lines of MM (Contains proteasome inhibitors and immunomodulatory therapies that progress or relapse during the most recent treatment or after the end of treatment). Note: The planned treatment plan for one or more cycles is "one-line treatment"; induction chemotherapy, stem cell transplantation, and maintenance treatment (if there is no disease progression between them), it is considered as a one-line treatment plan;

5. The patient have one or more measurable multiple myeloma lesion, must include one of the following conditions:

   • Serum M protein≥1.0 g/dL(10g/L)
   • Urine M protein≥200 mg/24h
   • Serum free light chain(sFLC): κ/λ FLC ratio is abnormal and affected FLC ≥10mg / dL

6. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination;

7. ECOG scores 0 - 1;

8. Echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no severe arrhythmia;

9. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.

10. Absolute neutrophil count ≥1.0 × 109 / L, platelet count ≥50 × 109 / L; total serum bilirubin ≤1.5mg / dl; serum ALT or AST less than 2.5 times the upper limit of normal; serum creatinine ≤2.0mg / dl;

11. No contraindications of peripheral blood apheresis;

12. Expected survival time > 12 weeks;.

13. Female subjects of childbearing age must have a negative urine / blood pregnancy test within 7 days before cell therapy and not be in lactation; female or male subjects of childbearing age need to take effective contraception throughout the study.

Exclusion criteria

1. Have a history of allergy to cell ular products;
2. Presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or any heart function Grade 3 (moderate) or Grade 4 (severe) heart disease (according to the New York Heart Association Function Classification method: NYHA); patients with a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina pectoris or other clinically significant heart disease within 12 months before enrollment;
3. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease;
4. Need to use any anticoagulant (except aspirin);
5. Patients requiring urgent treatment due to tumor progression or spinal cord compression;
6. Patients with CNS metastasis or symptoms of CNS involvement;
7. After allogeneic hematopoietic stem cell transplantation;
8. Plasma cell leukemia;
9. Received systemic anti-tumor treatment within 2 weeks before apheresis, and within 1 week before apheresis, prednisone (or equivalent amount of other corticosteroids) was applied in excess of 5 mg/d ;
10. Patients with autoimmune diseases, immunodeficiency, or other immunosuppressive agents;
11. Uncontrolled active infection;
12. Have used any CAR T cell products or other genetically modified T cell therapy before;
13. Live vaccination within 4 weeks before enrollment;
14. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV infected persons;
15. Have a history of alcoholism, drug addiction and mental illness;
16. Participated in any other clinical trial within 1 months;
17. The investigators believe that there are other circumstances that are not suitable for the trial.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

C-CAR088

Experimental group

Description:

Lymphocytes will be transduced with lentiviral vector containing CAR-BCMA gene.

Treatment:

Drug: C-CAR088