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Study of CT071 Injection in RRMM or PPCL

Primary Purpose

Multiple Myeloma, Primary Plasma Cell Leukemia

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Experimental: CAR-T cells Infusion
Sponsored by
Shanghai Changzheng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, primary plasma cell leukemia, CAR-T

Eligibility Criteria

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

Inclusion Criteria: Volunteer to participate in the clinical trial; fully understand and are informed of this trial and sign the informed consent form; Willing to follow and able to complete all trial procedures; Age ≥ 18 years, male or female; Patients with multiple myeloma who were resistant to at least two classes of anti-multiple myeloma drugs with at least one proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib, etc.) and at least one immunomodulatory agent (e.g., lenalidomide, pomalidomide, etc.) with relapse, progression, failure to achieve remission, or documented intolerable toxicity; Or patients with multiple myeloma who had failed at least three lines of therapy (required prior therapy containing at least one proteasome inhibitor and at least one immunomodulatory agent). Patients with secondary plasma-cell leukemia had received at least one line of therapy; Patients with primary plasma cell leukemia progressed after treatment with at least 1 regimen; Progressive disease at the time of enrollment according to the IMWG consensus for myeloma or plasma cell leukemia; Have any of the following evaluable conditions: Serum M-protein ≥ 5 g/L; 24-hour urine M-protein ≥ 200 mg; Abnormal serum free light chain (sFLC) ratio and affected FLC ≥ 100 mg/L in subjects with multiple myeloma who did not meet evaluable criteria for either serum or urine M-protein levels; Circulating plasma cells ≥ 5%; Estimated survival > 12 weeks; Eastern Cooperative Oncology Group (ECOG) score 0-2; Subjects had adequate organ function. Female subjects of childbearing potential must have a negative serum pregnancy test at screening, be willing to use a highly effective and reliable method of contraception within 1 year after receiving the trial treatment, and absolutely prohibit egg donation during the trial and within 1 year after receiving the trial treatment; Male subjects, if sexually active with a female of childbearing potential, are willing to use a highly effective and reliable method of contraception for 1 year after receiving trial treatment. All male subjects are absolutely prohibited from donating sperm during the trial and for 1 year after receiving the trial treatment. Exclusion Criteria: Pregnant or lactating females; Patients with a history of neurological disease, such as epilepsy, intracranial hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, memory impairment, spinal cord compression, psychiatric disease or any disease involving the central nervous system, or suspected central nervous system (CNS) metastasis; Patients with other incurable malignant tumors within 5 years or at the same time, except for those with very low degree of malignancy; Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, inflammatory bowel disease and other patients requiring long-term immunosuppressive therapy; Received allogeneic stem cell transplantation within two years prior to screening; Received autologous stem cell transplantation within 12 weeks prior to screening, or plan to receive autologous stem cell transplantation during the trial; Any uncontrolled disease or disorder with important clinical significance investigator considered not applicable for the study; Any active infection requiring systemic treatment (except prophylactic treatment) within 4 weeks prior to apheresis; Major surgery within 2 weeks prior to screening, or planning to undergo major surgery within 4 weeks after trial treatment (excluding cataract and other surgery under local anesthesia); Received treatment for the disease under study within 2 weeks prior to apheresis(or within five half-lives of the drug, whichever is shorter), including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulators, targeted therapy, radiotherapy, epigenetic therapy, etc.; Received anti-PD-1/PD-L1 monoclonal antibody or other investigational drug/invasive medical device within 4 weeksprior to apheresis; Vaccination with live attenuated vaccine or mRNA vaccine within 8 weeks and inactivated vaccine within 4 weeks before screening; Patients who are allergic or intolerant to CLD drugs, tocilizumab, or allergic to the ingredients of CT071 cell infusion preparation (DMSO); Or previous history of other severe allergies, such as anaphylactic shock; Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, cytomegalovirus (CMV) DNA, Epstein-Barr virus (EBV) DNA, hepatitis C virus (HCV) RNA, hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA; The toxicities caused by the previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except for alopecia and other tolerable events as judged by the investigator; Left ventricular ejection fraction (LVEF) < 50%; Oxygen saturation < 92% at room air; Received glucocorticoids within 7 days prior to apheresis, with the exception of inhaled glucocorticoids and physiologic replacement doses; Other conditions considered inappropriate for participation in this clinical trial by the investigator.

Sites / Locations

  • Shanghai Changzheng HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T cells Infusion

Arm Description

Biological: CART cells chimeric antigen receptor T cells

Outcomes

Primary Outcome Measures

DLT after CT071 infusion
Evaluate DLT and adverse events after CT071 infusion
AE of Neurotoxicity and cytokine release syndrome after CT071 infusion
Cytokine release syndrome(CRS)should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading,higher scores mean a worse outcome.
Adverse Events (AE) after CT071 infusion
An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cellassociated neurotoxicity syndrome (ICANS).

Secondary Outcome Measures

Level of CAR-T Cell Expansion (proliferation), and Persistence
Levels of cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Cytokines in the peripheral blood after CT071 infusion
Serum concentrations of interleukin (IL)-2, IL-6,IL-8,IL-10,interferon-gamma (IFN-γ), and TNF-α after CT071 infusion
Preliminary evaluation of immunogenicity
ADA positive rate
Overall response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria after CT071 infusion
ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria
Rate of very good partial response (VGPR) and above, complete response/stringent complete response (CR/sCR);
Rate of very good partial response (VGPR) and above defined as proportion of patients achieving VGPR or better based on IMWG defined response criteria; Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria.
Duration of response (DOR)
DOR is defined as the time from first achieving PR or better to confirmed disease progression or death from any cause.
Minimal residual disease (MRD) negative rate;
Minimal residual disease (MRD) negative rate is defined as the proportion of patients with VGPR or better who achieved 10-5 sensitivity of nucleated cell.
Time to response (TTR)
TTR defined as the time from the date of apheresis to the date of initial assessment of PR or better in patients with a best response assessment of partial response or better according to IMWG2016 criteria.
Progression-free survival (PFS)
PFS defined as the time from the date of apheresis of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first.
Overall survival (OS)
OS defined as the time from the date of apheresis of the subject to death from any cause.

Full Information

First Posted
April 3, 2023
Last Updated
September 19, 2023
Sponsor
Shanghai Changzheng Hospital
Collaborators
CARsgen Therapeutics Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05838131
Brief Title
Study of CT071 Injection in RRMM or PPCL
Official Title
A Clinical Trial to Explore the Safety and Efficacy of CT071 Injection in Patients With Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 28, 2023 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital
Collaborators
CARsgen 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
A Clinical Trial to Explore the Safety and Efficacy of CT071 injection in Patients with Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia
Detailed Description
This trial is a single-arm, open-label, dose-finding, first-in-human clinical trial. The main aim of this study is to preliminarily evaluate the safety and tolerability of CT071 after infusion, and explore the dose range of CT071 in patients with relapsed/refractory multiple myeloma or primary plasma cell leukemia, so as to determine the possible recommended therapeutic dose (RD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Primary Plasma Cell Leukemia
Keywords
multiple myeloma, primary plasma cell leukemia, CAR-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T cells Infusion
Arm Type
Experimental
Arm Description
Biological: CART cells chimeric antigen receptor T cells
Intervention Type
Drug
Intervention Name(s)
Experimental: CAR-T cells Infusion
Other Intervention Name(s)
Single Group Assignment
Intervention Description
Biological: chimeric antigen receptor T cells
Primary Outcome Measure Information:
Title
DLT after CT071 infusion
Description
Evaluate DLT and adverse events after CT071 infusion
Time Frame
Assessed from the date of first dose of study treatment until 21~28 days
Title
AE of Neurotoxicity and cytokine release syndrome after CT071 infusion
Description
Cytokine release syndrome(CRS)should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading,higher scores mean a worse outcome.
Time Frame
From first dose of study drug adminisration to end of treatment (up to 12 months)
Title
Adverse Events (AE) after CT071 infusion
Description
An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cellassociated neurotoxicity syndrome (ICANS).
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Secondary Outcome Measure Information:
Title
Level of CAR-T Cell Expansion (proliferation), and Persistence
Description
Levels of cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Time Frame
From first dose of study drug administration to 26 weeks
Title
Cytokines in the peripheral blood after CT071 infusion
Description
Serum concentrations of interleukin (IL)-2, IL-6,IL-8,IL-10,interferon-gamma (IFN-γ), and TNF-α after CT071 infusion
Time Frame
From first dose of study drug administration to 4 weeks
Title
Preliminary evaluation of immunogenicity
Description
ADA positive rate
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Overall response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria after CT071 infusion
Description
ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Rate of very good partial response (VGPR) and above, complete response/stringent complete response (CR/sCR);
Description
Rate of very good partial response (VGPR) and above defined as proportion of patients achieving VGPR or better based on IMWG defined response criteria; Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria.
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Duration of response (DOR)
Description
DOR is defined as the time from first achieving PR or better to confirmed disease progression or death from any cause.
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Minimal residual disease (MRD) negative rate;
Description
Minimal residual disease (MRD) negative rate is defined as the proportion of patients with VGPR or better who achieved 10-5 sensitivity of nucleated cell.
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Time to response (TTR)
Description
TTR defined as the time from the date of apheresis to the date of initial assessment of PR or better in patients with a best response assessment of partial response or better according to IMWG2016 criteria.
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Progression-free survival (PFS)
Description
PFS defined as the time from the date of apheresis of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first.
Time Frame
From first dose of study drug administration to end of treatment (up to 12 months)
Title
Overall survival (OS)
Description
OS defined as the time from the date of apheresis of the subject to death from any cause.
Time Frame
From first dose of study drug administration to death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Volunteer to participate in the clinical trial; fully understand and are informed of this trial and sign the informed consent form; Willing to follow and able to complete all trial procedures; Age ≥ 18 years, male or female; Patients with multiple myeloma who were resistant to at least two classes of anti-multiple myeloma drugs with at least one proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib, etc.) and at least one immunomodulatory agent (e.g., lenalidomide, pomalidomide, etc.) with relapse, progression, failure to achieve remission, or documented intolerable toxicity; Or patients with multiple myeloma who had failed at least three lines of therapy (required prior therapy containing at least one proteasome inhibitor and at least one immunomodulatory agent). Patients with secondary plasma-cell leukemia had received at least one line of therapy; Patients with primary plasma cell leukemia progressed after treatment with at least 1 regimen; Progressive disease at the time of enrollment according to the IMWG consensus for myeloma or plasma cell leukemia; Have any of the following evaluable conditions: Serum M-protein ≥ 5 g/L; 24-hour urine M-protein ≥ 200 mg; Abnormal serum free light chain (sFLC) ratio and affected FLC ≥ 100 mg/L in subjects with multiple myeloma who did not meet evaluable criteria for either serum or urine M-protein levels; Circulating plasma cells ≥ 5%; Estimated survival > 12 weeks; Eastern Cooperative Oncology Group (ECOG) score 0-2; Subjects had adequate organ function. Female subjects of childbearing potential must have a negative serum pregnancy test at screening, be willing to use a highly effective and reliable method of contraception within 1 year after receiving the trial treatment, and absolutely prohibit egg donation during the trial and within 1 year after receiving the trial treatment; Male subjects, if sexually active with a female of childbearing potential, are willing to use a highly effective and reliable method of contraception for 1 year after receiving trial treatment. All male subjects are absolutely prohibited from donating sperm during the trial and for 1 year after receiving the trial treatment. Exclusion Criteria: Pregnant or lactating females; Patients with a history of neurological disease, such as epilepsy, intracranial hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, memory impairment, spinal cord compression, psychiatric disease or any disease involving the central nervous system, or suspected central nervous system (CNS) metastasis; Patients with other incurable malignant tumors within 5 years or at the same time, except for those with very low degree of malignancy; Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, inflammatory bowel disease and other patients requiring long-term immunosuppressive therapy; Received allogeneic stem cell transplantation within two years prior to screening; Received autologous stem cell transplantation within 12 weeks prior to screening, or plan to receive autologous stem cell transplantation during the trial; Any uncontrolled disease or disorder with important clinical significance investigator considered not applicable for the study; Any active infection requiring systemic treatment (except prophylactic treatment) within 4 weeks prior to apheresis; Major surgery within 2 weeks prior to screening, or planning to undergo major surgery within 4 weeks after trial treatment (excluding cataract and other surgery under local anesthesia); Received treatment for the disease under study within 2 weeks prior to apheresis(or within five half-lives of the drug, whichever is shorter), including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulators, targeted therapy, radiotherapy, epigenetic therapy, etc.; Received anti-PD-1/PD-L1 monoclonal antibody or other investigational drug/invasive medical device within 4 weeksprior to apheresis; Vaccination with live attenuated vaccine or mRNA vaccine within 8 weeks and inactivated vaccine within 4 weeks before screening; Patients who are allergic or intolerant to CLD drugs, tocilizumab, or allergic to the ingredients of CT071 cell infusion preparation (DMSO); Or previous history of other severe allergies, such as anaphylactic shock; Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, cytomegalovirus (CMV) DNA, Epstein-Barr virus (EBV) DNA, hepatitis C virus (HCV) RNA, hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA; The toxicities caused by the previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except for alopecia and other tolerable events as judged by the investigator; Left ventricular ejection fraction (LVEF) < 50%; Oxygen saturation < 92% at room air; Received glucocorticoids within 7 days prior to apheresis, with the exception of inhaled glucocorticoids and physiologic replacement doses; Other conditions considered inappropriate for participation in this clinical trial by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Juan Du
Phone
+8615800706091
Email
changzheng_pg@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Du
Organizational Affiliation
Shanghai Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Du, Ph.D
Email
juan_du@live.com
First Name & Middle Initial & Last Name & Degree
Juan Du, Ph.D

12. IPD Sharing Statement

Learn more about this trial

Study of CT071 Injection in RRMM or PPCL

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