Clinical trial NCT03815383: 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: Relapsed or Refractory Multiple Myeloma
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2019-01-24
Enrollment: 12
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. Volunteered to participate in this study and signed informed consent.
2. Age 18-75 years old, male or female.
3. Meet the internationally accepted Criteria for the diagnosis of multiple myeloma (IMWG diagnostic criteria 2014).
4. Patients with relapsed or refractory multiple myeloma.
5. Subjects have one or more measurable multiple myeloma lesion, must include one of the following conditions:

   * Serum M protein≥1 g/dl(10g/L)
   * Urine M protein≥200 mg/24h
   * Serum free light chain(sFLC): κ/λ ratio abnormal and ≥10 mg/dl
6. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
7. At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy.
8. ECOG scores 0 - 1.
9. Normal cardiac diastolic function, left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography), no serious arrhythmia.
10. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
11. No contraindications of leukapheresis.
12. Expected survival \> 12 weeks.
13. Female subjects in childbearing age, their serum or urine pregnancy test must be negative,until 7 days before cell therapy and all subjects must agree to take effective contraceptive measures during the trial.

Exclusion Criteria:

1. Have a history of allergy to cellular products.
2. Any kind of these laboratory testing: including but not limited to,serum total bilirubin≧1.5mg/dl, serum ALT, AST≧2.5×ULN, serum creatinine≧2.0mg/dl, Hb (hemoglobin)\<80g/L, neutrophils\<1000/mm\^3, platelets≦50000/mm\^3 or platelet count maintained by transfusion.
3. Subjects with the clinically significant cardiovascular diseases.
4. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease.
5. Use any anticoagulant (except aspirin).
6. Patients requiring urgent treatment due to tumor progression or spinal cord compression.
7. Patients with active CNS involvement or clinical syndrome of MM meningeal involvement.
8. After allogeneic hematopoietic stem cell transplantation.
9. Plasma cell leukemia.
10. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy.
11. Uncontrolled active infection.
12. Prior treatment with CAR T therapy or any other genetically modified T cell therapy.
13. Live vaccine inoculation within four 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 one month.
17. The investigators believe that there are other circumstances that are not suitable for the trial.

Primary outcomes:
measure: Safety:TEAEs
timeFrame: 30 days
Secondary outcomes:
measure: ORR
timeFrame: 12 months
measure: PFS
timeFrame: 6 months, 12 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
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.