Clinical trial NCT04295018: A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma
Official title: A Phase # 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: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2020-03-04
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 study to evaluate the safety and efficacy of C-CAR088 in relapsed or refractory multiple myeloma patients.

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

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. Patients with a clear diagnosis of relapsed or refractory multiple myeloma
4. 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
5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination;
6. At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy.
7. ECOG scores 0 - 1;
8. Good cardiac and pulmonary organ function;
9. Expected survival time \> 12 weeks;.
10. 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 cellular products;
2. Laboratory testing occurs when: including but not limited to, serum total bilirubin ≥1.5mg / dl; serum ALT or AST is 2.5 times higher than the upper limit of normal value; serum creatinine ≥2.0mg / dl; hemoglobin \<80g / L; absolute neutrophil count \<1000 / mm3 or dependent on GCSF or Other growth factors can maintain the centriole count ≥1000 / mm²; platelet count \<50000 / mm³ or the above level can be maintained due to platelet transfusion;
3. 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;
4. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease;
5. Need to use any anticoagulant (except aspirin);
6. Patients requiring urgent treatment due to tumor progression or spinal cord compression;
7. Patients with CNS metastasis or symptoms of CNS involvement;
8. After allogeneic hematopoietic stem cell transplantation;
9. Plasma cell leukemia;
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. 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;
14. Have a history of alcoholism, drug addiction and mental illness;
15. Participated in any other clinical trial within 1 months;
16. The investigators believe that there are other circumstances that are not suitable for the trial.

Primary outcomes:
measure: The Incidence of adverse events (TEAEs) within 30 days after intravenous infusion of C-CAR088
timeFrame: 30 days
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 12 months
measure: Progression free survival (PFS)
timeFrame: 6 months#12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou
role: PRINCIPAL_INVESTIGATOR
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.