A Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in Patients With Relapsed/Refractory Extramedullary Multiple Myeloma
Primary Purpose
Extramedullary Multiple Myeloma
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Selinexor
CT103A
Sponsored by
About this trial
This is an interventional treatment trial for Extramedullary Multiple Myeloma focused on measuring CT103A, Selinexor
Eligibility Criteria
Inclusion Criteria:
Subjects must satisfy all the following criteria to be enrolled in the study:
- age ≥18 years old, male or female.
- Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 3 prior lines of therapy
- Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue(e.g., bone marrow biopsies, or plasmacytoma).
- Subjects with extramedullary myeloma require extramedullary lesions with a maximum diameter of ≥2cm
- ECOG score is ≤ 2
- Estimated life expectancy ≥ 12 weeks.
- Subjects should have adequate organ function:
- Absolute neutrophil count (ANC) ≥1×10^9 /L; absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L; hemoglobin ≥60 g/L.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
- Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
- Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
- SpO2 > 91%.
- Left ventricular ejection fraction (LVEF) ≥ 50%. 8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) from the date of the subject's informed consent to one year post CAR T cell infusion.
9. Subject must sign the informed consent form approved by the ethics board in person before starting any screening procedure.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
- Subjects who are known to be resistant to Selinexor;
- Subjects who need to use immunosuppressive agents for a long time due to graft-versus-host disease (GVHD) or autoimmune diseases.
- Subjects have received any anti-cancer treatment as follows: monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis, or anti-tumor treatments other than those listed above within 30 days before leukapheresis.
- Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
- Subjects with hypertension that cannot be controlled by medication
- Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
- Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
- Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
- Subjects with a history of organ transplantation.
- Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia)
- Subjects participated in another interventional clinical study within 1 month before signing the informed consent (ICF).
- Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis.
Positive for any of the following tests:
- Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood
- Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
- Human immunodeficiency virus (HIV) antibody
- Cytomegalovirus (CMV) DNA
- Treponema Pallidum antibody
- Pregnant or lactating women.
- Subjects with mental illness or consciousness disorder or disease of the central nervous system
- Other conditions that researchers consider inappropriate for enrollment.
Sites / Locations
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CT103A combined with Selinexor
Arm Description
All subjects will be assigned to two Selinexor dose groups of 20 mg/week and 40 mg/week after receiving a single dose infusion of CT103A.
Outcomes
Primary Outcome Measures
Progression-free survival (PFS)
The time from the start of CT103A treatment for the subjects to the first disease progression or death for any reason.
Objective response rate (ORR)
The percentage of subjects who achieved sCR、CR、VGPR、PR.
Duration of response (DOR) after administration
DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria
Secondary Outcome Measures
Overall survival (OS)
OS is measured from the date of the initial infusion of CT103A to the date of the participant's death.
Minimal Residual Disease (MRD) efficacy evaluation
MRD evaluation according to IMWG, including the proportion of subjects who achieved MRD negative and the duration of MRD negative.
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity
Pharmacokinetics - Cmax of CT103A
The maximum transgene level at Cmax fo CT103A
Pharmacokinetics - Tmax of CT103A
The maximum transgene level at Tmax fo CT103A
Pharmacokinetics - AUC0-28days of CT103A
Area under the curve of CT103A cells from time zero to Day 28 of CT103A
Pharmacokinetics - AUC0-90days of CT103A
Area under the curve of CT103A cells from time zero to Day 90 of CT103A
Pharmacokinetics of Selinexor
The changes of concentration of Selinexor in peripheral blood will be assessed.
PD endpoints
The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6
Health-related quality of life assessment
HRQoL will be assessed by the European Organization for Cancer Research and Treatment Quality of Life Questionnaire (EORTC-QLQ-C30)
Appraisal of life quality
Appraisal of life quality of the subjects will be assessed by the Quality of Life Multiple Myeloma Module Questionnaire (QLQ-MY20)
Evaluation of lymphocyte subsets
Lymphocyte subsets will be assessed by FACS
Concentration of immunoglobulins
The levels of Immunoglobulins in peripheral blood will be assessed to monitor changes at each time point
Full Information
NCT ID
NCT05201118
First Posted
January 5, 2022
Last Updated
May 17, 2022
Sponsor
Chunrui Li
Collaborators
Nanjing IASO Biotechnology Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05201118
Brief Title
A Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in Patients With Relapsed/Refractory Extramedullary Multiple Myeloma
Official Title
Phase I Clinical Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in the Treatment of Patients With Relapsed/Refractory Extramedullary Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Chunrui Li
Collaborators
Nanjing IASO Biotechnology 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
This study is a single-center, open Phase I study, to observe the effectiveness and safety of CT103A combined with different doses of Selinexor in patients with relapsed/refractory extramedullary multiple myeloma, and the pharmacokinetics of Selinexor and CT103A Kinetic and pharmacodynamic characteristics.
Detailed Description
In this study, two dose groups of 20 mg/week and 40 mg/week will be set for Selinexor, and the dose of CT103A is 1.0×106 cells/Kg. Subjects in all dose groups will firstly receive a single dose infusion of CT103A, at least 1 month post infusion and platelet recovery to ≥50×109/L. Then subjects began to take Selinexor once a week for one year. Each dose group level will include 8-10 subjects, and a total of 16-20 subjects are expected to be enrolled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extramedullary Multiple Myeloma
Keywords
CT103A, Selinexor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
The efficacy and safety, as well as the pharmacokinetic and pharmacodynamic characteristics of CT103A combined with different doses of Selinexor will be assessed in patients with relapsed/refractory extramedullary multiple myeloma. In this study, CT103A will be infused at the dose of 1.0×10^6 cells/Kg, while Selinexor was set as two dosage groups of 20 mg/week and 40 mg/week. Subjects in all dose groups received a single infusion of CT103A, and at least 1 month after the infusion of CT103A, Selinexor was administered orally once a week for one year when platelet count recovered to ≥50×10^9 /L. 8 to 10 subjects were enrolled at each dose group level, with a total of 16 to 20 subjects expected to be enrolled.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CT103A combined with Selinexor
Arm Type
Experimental
Arm Description
All subjects will be assigned to two Selinexor dose groups of 20 mg/week and 40 mg/week after receiving a single dose infusion of CT103A.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Intervention Description
Selinexor, 20 mg/tablet, is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1which is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM.
Intervention Type
Drug
Intervention Name(s)
CT103A
Intervention Description
CT103A consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that containing a unique CAR structure with a fully human single-chain variable fragment (scFv).
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
The time from the start of CT103A treatment for the subjects to the first disease progression or death for any reason.
Time Frame
1 year post CT103A infusion
Title
Objective response rate (ORR)
Description
The percentage of subjects who achieved sCR、CR、VGPR、PR.
Time Frame
1 year post CT103A infusion
Title
Duration of response (DOR) after administration
Description
DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria
Time Frame
1 year post CT103A infusion
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS is measured from the date of the initial infusion of CT103A to the date of the participant's death.
Time Frame
1 year post CT103A infusion
Title
Minimal Residual Disease (MRD) efficacy evaluation
Description
MRD evaluation according to IMWG, including the proportion of subjects who achieved MRD negative and the duration of MRD negative.
Time Frame
1 year post CT103A infusion
Title
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Description
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity
Time Frame
1 year post CT103A infusion
Title
Pharmacokinetics - Cmax of CT103A
Description
The maximum transgene level at Cmax fo CT103A
Time Frame
1 year post CT103A infusion
Title
Pharmacokinetics - Tmax of CT103A
Description
The maximum transgene level at Tmax fo CT103A
Time Frame
1 year post CT103A infusion
Title
Pharmacokinetics - AUC0-28days of CT103A
Description
Area under the curve of CT103A cells from time zero to Day 28 of CT103A
Time Frame
1 year post CT103A infusion
Title
Pharmacokinetics - AUC0-90days of CT103A
Description
Area under the curve of CT103A cells from time zero to Day 90 of CT103A
Time Frame
1 year post CT103A infusion
Title
Pharmacokinetics of Selinexor
Description
The changes of concentration of Selinexor in peripheral blood will be assessed.
Time Frame
1 year post CT103A infusion
Title
PD endpoints
Description
The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6
Time Frame
1 year post CT103A infusion
Title
Health-related quality of life assessment
Description
HRQoL will be assessed by the European Organization for Cancer Research and Treatment Quality of Life Questionnaire (EORTC-QLQ-C30)
Time Frame
1 year post CT103A infusion
Title
Appraisal of life quality
Description
Appraisal of life quality of the subjects will be assessed by the Quality of Life Multiple Myeloma Module Questionnaire (QLQ-MY20)
Time Frame
1 year post CAR-T cell infusion
Title
Evaluation of lymphocyte subsets
Description
Lymphocyte subsets will be assessed by FACS
Time Frame
1 year post CAR-T cell infusion
Title
Concentration of immunoglobulins
Description
The levels of Immunoglobulins in peripheral blood will be assessed to monitor changes at each time point
Time Frame
1 year post CAR-T cell infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must satisfy all the following criteria to be enrolled in the study:
age ≥18 years old, male or female.
Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 3 prior lines of therapy
Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue(e.g., bone marrow biopsies, or plasmacytoma).
Subjects with extramedullary myeloma require extramedullary lesions with a maximum diameter of ≥2cm
ECOG score is ≤ 2
Estimated life expectancy ≥ 12 weeks.
Subjects should have adequate organ function:
Absolute neutrophil count (ANC) ≥1×10^9 /L; absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L; hemoglobin ≥60 g/L.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
SpO2 > 91%.
Left ventricular ejection fraction (LVEF) ≥ 50%. 8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) from the date of the subject's informed consent to one year post CAR T cell infusion.
9. Subject must sign the informed consent form approved by the ethics board in person before starting any screening procedure.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
Subjects who are known to be resistant to Selinexor;
Subjects who need to use immunosuppressive agents for a long time due to graft-versus-host disease (GVHD) or autoimmune diseases.
Subjects have received any anti-cancer treatment as follows: monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis, or anti-tumor treatments other than those listed above within 30 days before leukapheresis.
Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
Subjects with hypertension that cannot be controlled by medication
Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
Subjects with a history of organ transplantation.
Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia)
Subjects participated in another interventional clinical study within 1 month before signing the informed consent (ICF).
Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis.
Positive for any of the following tests:
Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood
Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
Human immunodeficiency virus (HIV) antibody
Cytomegalovirus (CMV) DNA
Treponema Pallidum antibody
Pregnant or lactating women.
Subjects with mental illness or consciousness disorder or disease of the central nervous system
Other conditions that researchers consider inappropriate for enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chunrui Li
Phone
86-13647233185
Email
cunrui5650@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunrui Li
Organizational Affiliation
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hu Bei
ZIP/Postal Code
430000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunrui Li
Phone
+86 13647233185
Email
cunrui5650@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in Patients With Relapsed/Refractory Extramedullary Multiple Myeloma
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