Clinical trial NCT04714827: Targeting CD19 and BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Clinical Study to Evaluate the Safety and Effectiveness of CD19-BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Shanxi Province Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
First posted: 2021-01-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Evaluation the safety,tolerability, preliminary efficacy,and PK/PD of KQ-2003 CAR-T cells for the treatment of multiple myeloma

Detailed description: A non randomized study ,plans to enrollment 24 patients of B cell lymphoma ，divided into low, medium and high dose groups，to evaluate the safety and tolerability of KQ-2003 CAR-T cells immunotherapy in patients with relapsed or refractory B cell lymphoma ，to evaluate the preliminary efficacy and observe PK/PD parameters of KQ-2003 CAR-T cells immunotherapy in patients with relapsed or refractory multiple myeloma .

Eligibility criteria: Inclusion Criteria:

1. Agreed to participate in this study and signed informed consent, and willing to finish all the test procedure.
2. Age ≧ 18 years of age, gender not limited;
3. According to IMWG， diagnosis of multiple myeloma patients;
4. ECOG physical score ≤2 points ;
5. Relapsed multiple myeloma: disease progressed after received at least 3 lines treatment (must including the proteasome inhibitors and immune modulators); Refractory multiple myeloma: early treatment has never reached more than MR and curative effect; Or early treatment has reached more than MR and curative effect, but the subsequent treatment process or disease progress within 60 days after the last treatment ;
6. Have a measurable lesions in screening period (conform to one of the following standards: (1) the serum M protein: IgG protein≥10g/L, or IgA M protein ≥5g/L, or IgD M protein ≥5g/L; (2) M protein urine ≥200mg/24h; (3)If M protein in serum or urine cannot be measured,under the condition of the abnormal serum free light chain ratio,serum free light chain immunoglobulin or 100 mg/L;
7. Test results in screening period: (1) Hb≥60 g/L (7 days before the inspection without blood transfusion),PLT≥ 50 x 10 \^ 9 / L(7 days before the inspection without blood transfusion) ,ALC≥0.3×10\^9/L,ANC≥0.75×10\^9/L; (2)AST≤3ULN,ALT≤3ULN,TBIL≤2ULN；Ccr≥30 mL/min/1.73 m2;Correction of serum calcium ≤3.1mmol/L（≤12.5mg/dL）; LVEF≥40%； Baseline peripheral blood oxygen saturation ≥95%;
8. Female subjects with fertility ,pregnancy blood test results should be negative in screening period and before remove the lymphocyte ;
9. Expected to survival more than 3 months;

Exclusion Criteria:

1. The active hepatitis b, HBV - DNA detection lower limit of the subjects above research center; Hepatitis c virus (HCV) antibody positive and peripheral blood HCV - RNA positive subjects; Antibodies to HIV positive subjects; Early syphilis screening antibody positive;
2. The other clinical significance of active virus, bacterial infection, or failing to control systemic fungal infection;
3. Any instability of systemic disease, including but not limited to, unstable angina, cerebrovascular accident, or transient ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York heart association (NYHA) classification level III or higher congestive heart failure, drug control of serious arrhythmia, liver, kidney or metabolic diseases, as well as the standard treatment cannot control high blood pressure;
4. In past two years, because of autoimmune diseases such as crohn's disease, rheumatoid arthritis and systemic lupus erythematosus (sle), etc.) causing end-organ damage, or need systemic application of immunosuppressive drugs;
5. Had a history of the central nervous system diseases, such as epilepsy, serious brain damage, dementia, Parkinson's disease, psychosis,etc which influence the appraising of test,;
6. Diagnosed with other active malignancy in past five years(the basal or scaly skin cancer, superficial bladder cancer, breast cancer in situ, which has been cured and does not require follow-up treatment are not included );
7. Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s including accessories, DMSO ;
8. Patients with pregnancy or lactation, patients do not want to take effective contraceptive measures within 6months after infusion CAR-T cells;
9. The other situations that researchers determined doesn't fit to participate in this study.

Primary outcomes:
measure: DLT
timeFrame: Form infusion CAR-T cells to 28 days after infusion
measure: ORR
timeFrame: Form infusion CAR-T cells to 2 years after infusion
Secondary outcomes:
measure: Incidence of various types of adverse recation
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: PFS
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: DOR
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: OS
timeFrame: Form infusion CAR-T cells to subjects died，assessed up to 60 months
measure: Cmax
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Tmax
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: AUC（0-720d）
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL2 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL6 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL10 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of TNF-α level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IFN-γ level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
Other outcomes:
Locations:
city: Taiyuan
country: China
facility: Hematology Department of ShanXi Cancer Hospital
state: Shanxi
Study officials:
affiliation: Hematology Department of ShanXi Cancer Hospital
name: Liping Su, M.D.
role: PRINCIPAL_INVESTIGATOR
References: