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

A Clinical Study to Evaluate the Safety and Effectiveness of CD19-BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: KQ-2003 CAR-T cells

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liping Su, M.D.; Phone Number: +86 13835158122; Email: sulp2005@sohu.com

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Hematology Department of ShanXi Cancer Hospital
      • Contact: Tao Guan, PhD; Phone Number: +8613509717461; Email: 395714554@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose Group; 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.	Biological: KQ-2003 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and BCMA，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion KQ-2003 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection; CD19-BCMA CAR-T Cells
Experimental: Middle Dose Group; 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.	Biological: KQ-2003 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and BCMA，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion KQ-2003 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection; CD19-BCMA CAR-T Cells
Experimental: High Dose Group; 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.	Biological: KQ-2003 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and BCMA，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion KQ-2003 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection; CD19-BCMA CAR-T Cells
Experimental: Amplification Dose Group; 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.	Biological: KQ-2003 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and BCMA，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion KQ-2003 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection; CD19-BCMA CAR-T Cells

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanxi Province Cancer Hospital
• Collaborators: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
• Investigators: Principal Investigator: Liping Su, M.D., Hematology Department of ShanXi Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2021
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: CAR-T SXZL03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan to Share Clinical Study Report within six months after the study completed
• IPD Sharing Time Frame: Within six months after the study completed
• IPD Sharing Access Criteria: Research site
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No