Clinical trial NCT06503107: Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of R/RMM
Official title: A Multicenter Clinical Study on the Safety and Efficacy of Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: CAR-T
BCMA
Relapsed / Refractory multiple myeloma
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Hebei Taihe Chunyu Biotechnology Co., Ltd
name: Huazhong University of Science and Technology Union Shenzhen Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
First posted: 2024-07-16
Enrollment: 60
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: To explore the safety and efficacy of nanobody-based BCMA-targeting biepitope CAR-T cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive CAR-T cell therapy. Patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

Detailed description: This study is a multicenter, open-label, prospective, single-arm clinical study with patients with relapsed/refractory multiple myeloma as the test subjects, in order to evaluate the safety and efficacy of nanobody-based biepitope CAR-T cells targeting BCMA in the treatment of R/RMM, and to collect CAR-T PK/PD indicators. The structure of BCMA target CAR-T is designed to identify two different epitopes of BCMA protein with two recognition domains, in order to killig MM cells without secreting more pro-inflammatory factors and avoiding escape caused by the limitations of single BCMA antigen recognition.

Eligibility criteria: Inclusion Criteria:

* Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
* Aged ≥ 18 years and ≤ 75 years.
* Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).
* Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.
* Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.
* Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.
* ECOG score 0-2 points.
* HGB≥70g/L，PLT≥30×10\^9/L.
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) \>30 ml/min；
  2. Left ventricular ejection fraction (LVEF) ≥50%,
  3. Baseline peripheral oxygen saturation \> 90%;
  4. Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

Exclusion Criteria:

* Previous diagnosis and treatment of other malignancies within 3 years;
* Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF \<30% or LVEF \<50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
* Patients with active GVHD;
* Patients with a history of severe pulmonary impairment disease;
* Combined with other malignant tumors in the advanced stage;
* Co-infection with severe or persistent infection that cannot be effectively controlled;
* Combined with severe autoimmune disease or congenital immunodeficiency;
* Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA ≥ 500 IU/ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
* Human immunodeficiency virus (HIV) infection or syphilis infection;
* Patients with a history of severe allergy to biological products (including antibiotics);
* Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
* Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
* Other conditions considered inappropriate by the researcher.

Primary outcomes:
measure: Incidence of Treatment-related Adverse Events
timeFrame: within 3 years after infusion
measure: Overall response rate (ORR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM
timeFrame: within 3 years after infusion
measure: The rates of complete response (CR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM
timeFrame: within 3 years after infusion
measure: Very good partial response (VGPR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM
timeFrame: within 3 years after infusion
measure: Partial response rate (PR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM
timeFrame: within 3 years after infusion
measure: Stable diseases (SD) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM
timeFrame: within 3 years after infusion
Secondary outcomes:
measure: Overall survival (OS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma
timeFrame: within 3 years after infusion
measure: Progression-free survival (PFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma
timeFrame: within 3 years after infusion
measure: Event-free survival (EFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma
timeFrame: within 3 years after infusion
Other outcomes:
measure: In vivo expansion and survival of nanobody-based biepitope CAR-T cells targeting BCMA
timeFrame: within 3 years after infusion
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
References:
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