Clinical trial NCT04322292: A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma
Official title: A Phase Ⅰ Study Evaluating Safety and Efficacy of C-CAR088 Treatment in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Safety: The incidence of treatment-emergent adverse events (TEAEs)
timeFrame: 30 days
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 12 months
measure: Progression free survival (PFS)
timeFrame: 6 months、12 months
measure: The CART cell duration in vivo
timeFrame: 12 months
measure: The soluble BCMA changes in peripheral blood
timeFrame: 12 months
Other outcomes:
Locations:
city: TianJin
country: China
facility: InstituteHBDH
Study officials:
References:
citation: Qu X, An G, Sui W, Wang T, Zhang X, Yang J, Zhang Y, Zhang L, Zhu D, Huang J, Zhu S, Yao X, Li J, Zheng C, Zhu K, Wei Y, Lv X, Lan L, Yao Y, Zhou D, Lu P, Qiu L, Li J. Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. J Immunother Cancer. 2022 Sep;10(9):e005145. doi: 10.1136/jitc-2022-005145.