Clinical trial NCT04706936: Novel BCMA-targeted CAR-T Cell Therapy for Multiple Myeloma
Official title: Novel BCMA-targeted CAR-T Cell Therapy for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: BCMA
Chimeric antigen receptor T cell
Adoptive cell therapy
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Carbiogene Therapeutics Co. Ltd.
First posted: 2021-01-13
Enrollment: 25
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 study evaluates the safety and efficacy of novel BCMA-targeted CAR-T cell therapy (CBG-002) for patients with relapsed or refractory multiple myeloma (r/r MM). CBG-002 is designed based on the fourth-generation of CAR-T techonology.


Eligibility criteria: Inclusion Criteria:

1. Patients with relapsed/refractory multiple myeloma aged 18-75 years;
2. BCMA expression ≥50% in bone marrow samples confirmed by Flow Cytometry or IHC is positive for BCMA expression;
3. Relapsed/refractory patients who meet the following conditions:

   1. Ineffective or disease progression after receiving bortezomib (proteasome inhibitor) and lenalidomide for 3 courses;
   2. Ineffective or disease progression after receiving the original treatment plan for 3 courses;
   3. The interval between the last treatment and disease progression is more than 30 days;
   4. There is currently no indication for hematopoietic stem cell transplantation, or the patient refuses to do hematopoietic stem cell transplantation;
   5. The definition of disease progression refers to the "2014 IMWG Standards", and at least meets the following 1 items:

   e.1 Serum M protein ≥ 0.5 g/dL;

   e.2 Urine M protein ≥ 200 mg/24 h;

   e.3 If the serum FLC ratio is abnormal, the patient's FLC level ≥ 10 mg/dL (100 mg/L);

   e.4 Evaluable plasmacytoma confirmed by biopsy;

   e.5 Increase in the proportion of bone marrow plasma cells ≥25% (absolute increase ≥10%);

   e.6 Bone marrow plasma cells account for 30% of the total bone marrow cells;
4. Estimated survival time\> 12 weeks;
5. The disease status can be assessed and meet at least one of the following:

   1. Serum M-protein ≥10 g/L;
   2. 24h urine M-protein ≥200mg;
   3. Serum FLC≥5mg/dL;
   4. Plasma cell tumors that can be assessed by testing or images;
   5. The proportion of bone marrow plasma cells ≥ 30%;
6. ECOG physical status score 0-1;
7. Have enough venous access for apheresis or venous blood collection, and there are no other contraindications for blood cell separation;
8. WBC ≥ 1.5×109/L; PLT ≥ 45×109/L;
9. Serum creatinine ≤ 1.5 upper limit of normal (ULN) ;
10. ALT ≤ 2.5 ULN, AST ≤ 2.5 ULN.

All laboratory test results within the above range should have no ongoing continuous supportive treatment.

Exclusion Criteria:

-

Subjects who meet any of the following criteria cannot be selected for this study:

1. Systemic treatment such as lymphatic depletion with cyclophosphamide and fludarabine within 2 weeks before enrollment or single cell collection, or cell therapy within 8 weeks before treatment;
2. HCV or HIV positive; any uncontrollable active infection, including active tuberculosis, HBV DNA level ≥1×103 copies/mL;
3. Active infections occurred within 72 hours before cleansing; as long as there is no evidence of active infection and antibiotics are not in the list of prohibited drugs, subjects who continue to use preventive antibiotics, antifungal drugs or antiviral drugs are not excluded;
4. The current systemic use of cyclosporine or steroid drugs such as dexamethasone, recent or current use of inhaled steroids is not excluded;
5. Renal insufficiency, serum creatinine\>1.5 upper limit of normal (ULN);
6. Liver insufficiency, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)\>2.5 times ULN and direct bilirubin\>1.5 times ULN;
7. Hyponatremia, blood sodium \<125 mmol/L;
8. Baseline serum potassium \<3.5 mmol/L (potassium supplementation can be given before participating in the study, and serum potassium recovery above this standard is not excluded);
9. Pregnant or lactating women;
10. Other serious diseases that may restrict subjects from participating in this trial (such as central nervous system disease, severe heart insufficiency, myocardial obstruction or unstable arrhythmia or unstable angina, gastric ulcer in the past 6 months , Active autoimmune diseases, etc.).

Primary outcomes:
measure: Rate of grade 3 or 4 treatment related adverse effect
timeFrame: 24 weeks after last dose of CAR-T treatment
measure: Overall response rate (ORR) after treated by CAR-T treatment
timeFrame: up to 2 years after CAR-T treatment
Secondary outcomes:
measure: Pharmacokinetics of CAR-T cells (implantation endpoint)
timeFrame: up to 2 years after CAR-T treatment
measure: Overall survival
timeFrame: up to 2 years after CAR-T treatment
measure: Progression free survival
timeFrame: up to 2 years after CAR-T treatment
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
name: Wenbin Qian
role: PRINCIPAL_INVESTIGATOR
References: