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

NCT04714827 | Unknown Phase 1

• 1 other identifier: CAR-T SXZL03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Incidence of various types of adverse recation

  Form infusion CAR-T cells to 2 years after infusion

• PFS

  Form infusion CAR-T cells to 2 years after infusion

• DOR

  Form infusion CAR-T cells to 2 years after infusion

• OS

  Form infusion CAR-T cells to subjects died，assessed up to 60 months

• 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

Study Arms (4)

Low Dose Group

EXPERIMENTAL

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

Middle Dose Group

EXPERIMENTAL

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

High Dose Group

EXPERIMENTAL

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

Amplification Dose Group

EXPERIMENTAL

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

Interventions

KQ-2003 CAR-T cells BIOLOGICAL

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 .

Also known as: Fluorine dara marina injection, Cyclophosphamide injection, CD19-BCMA CAR-T Cells

Amplification Dose Group; High Dose Group; Low Dose Group; Middle Dose Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agreed to participate in this study and signed informed consent, and willing to finish all the test procedure.
• Age ≧ 18 years of age, gender not limited;
• According to IMWG， diagnosis of multiple myeloma patients;
• ECOG physical score ≤2 points ;
• 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 ;
• 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;
• 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%;
• Female subjects with fertility ,pregnancy blood test results should be negative in screening period and before remove the lymphocyte ;
• Expected to survival more than 3 months;

You may not qualify if:

• 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;
• The other clinical significance of active virus, bacterial infection, or failing to control systemic fungal infection;
• 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;
• 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;
• 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,;
• 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 );
• Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s including accessories, DMSO ;
• Patients with pregnancy or lactation, patients do not want to take effective contraceptive measures within 6months after infusion CAR-T cells;
• The other situations that researchers determined doesn't fit to participate in this study.

Sponsors & Collaborators

• Shanxi Province Cancer Hospital: lead
• Novatim Immune Therapeutics (Zhejiang) Co., Ltd.: collaborator

Study Sites (1)

Hematology Department of ShanXi Cancer Hospital

Taiyuan, Shanxi, 030013, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Liping Su, M.D.

  Hematology Department of ShanXi Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liping Su, M.D.

CONTACT

13835158122; sulp2005@sohu.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 19, 2021
• Study Start: January 22, 2021
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2025
• Last Updated: December 29, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within six months after the study completed
• Access Criteria: Research site

Locations

CN (1)