Extramedullary Multiple Myeloma
Conditions
Keywords
CT103A, Selinexor
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.
Interventions
DRUGSelinexor
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.
DRUGCT103A
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).
Sponsors
Nanjing IASO Biotechnology Co., Ltd.
Chunrui Li
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must satisfy all the following criteria to be enrolled in the study: 1. age ≥18 years old, male or female. 2. Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 3 prior lines of therapy 3. 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). 4. Subjects with extramedullary myeloma require extramedullary lesions with a maximum diameter of ≥2cm 5. ECOG score is ≤ 2 6. Estimated life expectancy ≥ 12 weeks. 7. Subjects should have adequate organ function: <!-- --> 1. 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. 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN. 3. Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min. 4. Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN. 5. SpO2 \> 91%. 6. 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: 1. Subjects who are known to be resistant to Selinexor; 2. Subjects who need to use immunosuppressive agents for a long time due to graft-versus-host disease (GVHD) or autoimmune diseases. 3. 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. 4. 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. 5. Subjects with hypertension that cannot be controlled by medication 6. 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. 7. 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. 8. 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. 9. Subjects with a history of organ transplantation. 10. 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) 11. Subjects participated in another interventional clinical study within 1 month before signing the informed consent (ICF). 12. Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis. 13. 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 14. Pregnant or lactating women. 15. Subjects with mental illness or consciousness disorder or disease of the central nervous system 16. Other conditions that researchers consider inappropriate for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 1 year post CT103A infusion | 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) | 1 year post CT103A infusion | The percentage of subjects who achieved sCR、CR、VGPR、PR. |
| Duration of response (DOR) after administration | 1 year post CT103A infusion | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Cmax of CT103A | 1 year post CT103A infusion | The maximum transgene level at Cmax fo CT103A |
| Pharmacokinetics - Tmax of CT103A | 1 year post CT103A infusion | The maximum transgene level at Tmax fo CT103A |
| Pharmacokinetics - AUC0-28days of CT103A | 1 year post CT103A infusion | Area under the curve of CT103A cells from time zero to Day 28 of CT103A |
| Pharmacokinetics - AUC0-90days of CT103A | 1 year post CT103A infusion | Area under the curve of CT103A cells from time zero to Day 90 of CT103A |
| Pharmacokinetics of Selinexor | 1 year post CT103A infusion | The changes of concentration of Selinexor in peripheral blood will be assessed. |
| Overall survival (OS) | 1 year post CT103A infusion | OS is measured from the date of the initial infusion of CT103A to the date of the participant's death. |
| Health-related quality of life assessment | 1 year post CT103A infusion | HRQoL will be assessed by the European Organization for Cancer Research and Treatment Quality of Life Questionnaire (EORTC-QLQ-C30) |
| Appraisal of life quality | 1 year post CAR-T cell infusion | 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 | 1 year post CAR-T cell infusion | Lymphocyte subsets will be assessed by FACS |
| Concentration of immunoglobulins | 1 year post CAR-T cell infusion | The levels of Immunoglobulins in peripheral blood will be assessed to monitor changes at each time point |
| PD endpoints | 1 year post CT103A infusion | The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6 |
| Minimal Residual Disease (MRD) efficacy evaluation | 1 year post CT103A infusion | 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 | 1 year post CT103A infusion | 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 |
Countries
China
Contacts
Primary ContactChunrui Li
Outcome results
None listed