Targeting CD19 and BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma

Phase 1

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Biological: KQ-2003 CAR-T cells

• Registration Number: NCT04714827
• Lead Sponsor: Shanxi Province Cancer Hospital

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 .

Study Timeline

• Study First Submitted: 2021-01-07
• Study First Submitted QC: 2021-01-15
• Study First Posted: 2021-01-19
• Study Start: 2021-01-22
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-26
• Last Update Posted: 2023-12-29
• Primary Completion: 2024-09-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Low Dose Group	KQ-2003 CAR-T cells	KQ-2003 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 1.0×10\^6 CAR+T cells/kg.
Amplification Dose Group	KQ-2003 CAR-T cells	KQ-2003 CAR-T cells injection, infused only once.After determined maximum tolerated dose,15 subjects of amplification dose group will be intravenously infuse with 1.0-5.0×10\^6 CAR+Tcells/kg.
Middle Dose Group	KQ-2003 CAR-T cells	KQ-2003 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 2.5×10\^6 CAR+T cells/kg.
High Dose Group	KQ-2003 CAR-T cells	KQ-2003 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 5.0×10\^6 CAR+T cells/kg.

Primary Outcome Measures

Name	Time	Method
DLT	Form infusion CAR-T cells to 28 days after infusion	Observe wether dose limiting toxicity will happened in dose escalation phase
ORR	Form infusion CAR-T cells to 2 years after infusion	The overall response rate after CAR-T Cells immunotherapy

Secondary Outcome Measures

Name	Time	Method
OS	Form infusion CAR-T cells to subjects died，assessed up to 60 months	Overall survival
Incidence of various types of adverse recation	Form infusion CAR-T cells to 2 years after infusion	According to CTCAE 5.0, record the level , type of adverse events, evaluat the correlation of CD19-BCMA CAR-T cells
PFS	Form infusion CAR-T cells to 2 years after infusion	Progression-free surial
DOR	Form infusion CAR-T cells to 2 years after infusion	Duration of Response
Cmax	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	By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined
Tmax	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	The maximum concentration of time
Concentration of IL2 level	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	The levels of cytokines（IL2 ）in peripheral blood and bone marrow
AUC（0-720d）	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	Area under the plasma concentration versus time curve
Concentration of IL6 level	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	The levels of cytokines（ IL6 ）in peripheral blood and bone marrow
Concentration of IL10 level	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	The levels of cytokines（IL10 ）in peripheral blood and bone marrow
Concentration of TNF-α level	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	The levels of cytokines（TNF-α ）in peripheral blood and bone marrow
Concentration of IFN-γ level	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	The levels of cytokines（IFN-γ ）in peripheral blood and bone marrow

Trial Locations

Locations (1)

Hematology Department of ShanXi Cancer Hospital; 🇨🇳 Taiyuan, Shanxi, China