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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19-CD22 CAR-T cells
Sponsored by
Shanxi Province Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hematology Department of ShanXi Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Low Dose Group

Middle Dose Group

High Dose Group

Amplification Dose Group

Arm Description

CD19-BCMA 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.

CD19-BCMA 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.

CD19-BCMA 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.

CD19-BCMA 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.

Outcomes

Primary Outcome Measures

DLT
Observe wether dose limiting toxicity will happened in dose escalation phase
ORR
The overall response rate after CAR-T Cells immunotherapy

Secondary Outcome Measures

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
PFS
Progression-free surial
DOR
Duration of Response
OS
Overall survival
Cmax
By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined
Tmax
The maximum concentration of time
AUC(0-720d)
Area under the plasma concentration versus time curve
Concentration of IL2 level
The levels of cytokines(IL2 )in peripheral blood and bone marrow
Concentration of IL6 level
The levels of cytokines( IL6 )in peripheral blood and bone marrow
Concentration of IL10 level
The levels of cytokines(IL10 )in peripheral blood and bone marrow
Concentration of TNF-α level
The levels of cytokines(TNF-α )in peripheral blood and bone marrow
Concentration of IFN-γ level
The levels of cytokines(IFN-γ )in peripheral blood and bone marrow

Full Information

First Posted
January 7, 2021
Last Updated
January 17, 2021
Sponsor
Shanxi Province Cancer Hospital
Collaborators
Shanghai Ultra-T Immune Therapeutics Co. LTD
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1. Study Identification

Unique Protocol Identification Number
NCT04714827
Brief Title
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

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2021 (Anticipated)
Primary Completion Date
January 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanxi Province Cancer Hospital
Collaborators
Shanghai Ultra-T Immune Therapeutics Co. LTD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Evaluation the safety,tolerability, preliminary efficacy,and PK/PD of CD19-BCMA 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 CD19-BCMA CAR - T cells immunotherapy in patients with relapsed or refractory B cell lymphoma ,to evaluate the preliminary efficacy and observe PK/PD parameters of CD19-BCMA CAR - T cells immunotherapy in patients with relapsed or refractory multiple myeloma .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Dose Group
Arm Type
Experimental
Arm Description
CD19-BCMA 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.
Arm Title
Middle Dose Group
Arm Type
Experimental
Arm Description
CD19-BCMA 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.
Arm Title
High Dose Group
Arm Type
Experimental
Arm Description
CD19-BCMA 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.
Arm Title
Amplification Dose Group
Arm Type
Experimental
Arm Description
CD19-BCMA 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.
Intervention Type
Biological
Intervention Name(s)
CD19-CD22 CAR-T cells
Other Intervention Name(s)
Fluorine dara marina injection, Cyclophosphamide injection
Intervention Description
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 CD19-BCMA CAR-T cells .
Primary Outcome Measure Information:
Title
DLT
Description
Observe wether dose limiting toxicity will happened in dose escalation phase
Time Frame
Form infusion CAR-T cells to 28 days after infusion
Title
ORR
Description
The overall response rate after CAR-T Cells immunotherapy
Time Frame
Form infusion CAR-T cells to 2 years after infusion
Secondary Outcome Measure Information:
Title
Incidence of various types of adverse recation
Description
According to CTCAE 5.0, record the level , type of adverse events, evaluat the correlation of CD19-BCMA CAR-T cells
Time Frame
Form infusion CAR-T cells to 2 years after infusion
Title
PFS
Description
Progression-free surial
Time Frame
Form infusion CAR-T cells to 2 years after infusion
Title
DOR
Description
Duration of Response
Time Frame
Form infusion CAR-T cells to 2 years after infusion
Title
OS
Description
Overall survival
Time Frame
Form infusion CAR-T cells to subjects died,assessed up to 60 months
Title
Cmax
Description
By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined
Time Frame
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
Title
Tmax
Description
The maximum concentration of time
Time Frame
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
Title
AUC(0-720d)
Description
Area under the plasma concentration versus time curve
Time Frame
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
Title
Concentration of IL2 level
Description
The levels of cytokines(IL2 )in peripheral blood and bone marrow
Time Frame
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
Title
Concentration of IL6 level
Description
The levels of cytokines( IL6 )in peripheral blood and bone marrow
Time Frame
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
Title
Concentration of IL10 level
Description
The levels of cytokines(IL10 )in peripheral blood and bone marrow
Time Frame
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
Title
Concentration of TNF-α level
Description
The levels of cytokines(TNF-α )in peripheral blood and bone marrow
Time Frame
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
Title
Concentration of IFN-γ level
Description
The levels of cytokines(IFN-γ )in peripheral blood and bone marrow
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liping Su, M.D.
Phone
13835158122
Ext
+86
Email
sulp2005@sohu.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liping Su, M.D.
Organizational Affiliation
Hematology Department of ShanXi Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hematology Department of ShanXi Cancer Hospital
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tao Guan, PhD
Phone
+8613509717461
Email
395714554@qq.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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