Clinical trial NCT05181501: A Study of Fully Human BCMA CAR-T (CT103A) in Patients With Newly Diagnosed High-risk Multiple Myeloma (FUMANBA-2)
Official title: A Multi-center Clinical Study of Fully Human BCMA Chimeric Antigen Receptor Autologous T (CAR-T) Cell Injection (CT103A) in the Treatment of Newly Diagnosed Subjects With High-risk Multiple Myeloma (FUMANBA-2)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: newly diagnosed
multiple myeloma
treatment naive
CAR-T
Lead sponsor: Nanjing IASO Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a multi-center, single-arm clinical study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamic characteristics of CT103A as the first-line treatment in newly diagnosed high-risk multiple myeloma subjects with induction chemotherapy as bridging therapy.

Detailed description: Before enrollment, subjects will receive chemotherapy regimen of either Bortezomib-Lenalidomide-Dexamethasone (VRD), Bortezomib-Cyclophosphamide-Dexamethasone (PCD) or Bortezomib-Adriamycin-Dexamethasone (PAD) as induction therapy for 3 cycles. Evaluation will be made after 2 cycles of chemotherapy. If the subject is not intended to have stem cell transplantation or unsuitable for autologous hematopoietic stem cell transplantation (ASCT) as judged by the investigator, he/she will receive the 3rd cycle of chemotherapy. If the subject meets the inclusion criteria, he/she will be enrolled in the study.

Peripheral blood mononuclear cell (PBMC) will be collected to manufacture CT103A. After PBMC collection, the subject will receive another cycle of chemotherapy and evaluated. Lymphodepletion with fludarabine and cyclophosphamide will be performed for three consecutive days. After 1-day rest, subjects will receive a single infusion of CT103A at 1.0 ×10\^6 /kg. Subjects will be followed in the study for a minimum of 2 years after CT103A infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT103A infusion.

Eligibility criteria: Inclusion Criteria:

1. 18 to 70 years old, male or female;
2. Newly diagnosed as high-risk multiple myeloma:

   * Revised Multiple Myeloma International Staging System (R-ISS) stage 3;
   * Double-hit or triple-hit according to FISH test.
3. Presence of measurable lesions during screening according to any of the following criteria:

   * The proportion of primitive naive or monoclonal plasma cells ≥ 5% by bone marrow cytology, bone marrow biopsy histology or flow cytometry;
   * Serum monoclonal protein (M-protein) level: M protein ≥10 g/L for IgG type, M protein ≥5g/L for IgA, IgD, IgM, and IgE type;
   * Urine M protein level ≥200 mg/24 hours;
   * Light chain multiple myeloma without measurable lesions in serum or urine: the affected serum free light chain ≥100 mg/L with abnormal serum κ/λ free light chain ratio;
4. ECOG score of 0 or 1;
5. Expected survival time ≥ 12 weeks;
6. Subjects must have appropriate organ functions and meet all the following laboratory test requirements before enrollment:

   * Hematology: Absolute neutrophil count (ANC) ≥ 1×10\^9/L (prior growth factor support is allowed, but supportive treatment within 7 days before laboratory test is not allowed); Absolute lymphocyte count (ALC) )≥0.3×10\^9/L; platelets≥75×10\^9/L (blood transfusion support within 7 days before laboratory test is not allowed); hemoglobin ≥60 g/L (without red blood cell \[RBC\] transfusion within 7 days before laboratory test; recombinant human erythropoietin is allowed);
   * Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN); serum total bilirubin≤1.5×ULN;
   * Renal function: creatinine clearance calculated according to Cockcroft-Gault formula≥ 40 ml/min.
   * Coagulation function: fibrinogen ≥1.0 g/L; activated partial thromboplastin time≤1.5×ULN, prothrombin time (PT)≤1.5×ULN;
   * Blood oxygen saturation\>91%;
   * Left ventricular ejection fraction (LVEF) ≥50%;
7. Subjects and their spouses agree to take effective tools or contraceptive measures (safe period contraception is not included) from the time the subject signs the informed consent form until one year after the CAR-T cell infusion.

Exclusion Criteria:

1. Patient who needs chronic use of immunosuppressive agents;
2. Patient with hypertension that cannot be controlled by medication;
3. Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade III), severe arrhythmia;
4. Unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney or metabolic diseases that require drug treatment;
5. Patients with malignant tumors other than multiple myeloma within 5 years before screening, excluding fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, and those after radical resection Ductal carcinoma in situ of breast;
6. Patient with a history of solid organ transplantation;
7. Patient who is suspected with or with symptoms of central nervous system invasion by plasma cell tumors;
8. Multiple myeloma patients with plasma cell leukemia;
9. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and detectable hepatitis B virus (HBV) DNA in peripheral blood; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus ( HCV) RNA positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA test positive; syphilis test positive;
10. Women who are pregnant or breastfeeding;
11. Patient with mental illness or disturbance of consciousness or central nervous system disease;
12. Major surgery history within 2 weeks before entering the study, or scheduled surgery during the study period or within 2 weeks after the study treatment;
13. Other situations considered unsuitable by the investigator.

Primary outcomes:
measure: Proportion of Minimal Residual Disease (MRD)-negative subjects
timeFrame: Up to 2 years after CT103A infusion
measure: Median progression-free survival (mPFS)
timeFrame: Up to 2 years after CT103A infusion
Secondary outcomes:
measure: Best overall response (BOR)
timeFrame: Up to 2 years after CT103A infusion
measure: Median survival (mOS)
timeFrame: Up to 2 years after CT103A infusion
measure: Event-free survival (EFS)
timeFrame: Up to 2 years after CT103A infusion
measure: Duration of response (DOR)
timeFrame: Up to 2 years after CT103A infusion
measure: Safety endpoint
timeFrame: Up to 2 years after CT103A infusion
measure: Pharmacokinetic(PK) endpoint
timeFrame: Up to 90 days after CT103A infusion
measure: PK endpoint - Tmax
timeFrame: Up to 90 days after CT103A infusion
measure: PK endpoint - AUC 0 to 28d and AUC 0 to 90d
timeFrame: Up to 90 days after CT103A infusion
measure: Levels of Soluable BCMA
timeFrame: Up to 90 days after CT103A infusion
measure: PD endpoint
timeFrame: Up to 90 days after CT103A infusion
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Lijuan Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Bing Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: