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
Overview
- Phase
- Phase 1
- Intervention
- Selinexor
- Conditions
- Extramedullary Multiple Myeloma
- Sponsor
- Chunrui Li
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
- Last Updated
- 3 years ago
Overview
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.
Investigators
Chunrui Li
Professor
Tongji Hospital
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.
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.
Arms & Interventions
CT103A combined with Selinexor
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: Selinexor
CT103A combined with Selinexor
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: CT103A
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: 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)
Time Frame: 1 year post CT103A infusion
The percentage of subjects who achieved sCR、CR、VGPR、PR.
Duration of response (DOR) after administration
Time Frame: 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 Outcomes
- Pharmacokinetics - Tmax of CT103A(1 year post CT103A infusion)
- Pharmacokinetics - AUC0-28days of CT103A(1 year post CT103A infusion)
- Health-related quality of life assessment(1 year post CT103A infusion)
- Overall survival (OS)(1 year post CT103A infusion)
- Minimal Residual Disease (MRD) efficacy evaluation(1 year post CT103A infusion)
- Pharmacokinetics - Cmax of CT103A(1 year post CT103A infusion)
- Concentration of immunoglobulins(1 year post CAR-T cell infusion)
- Pharmacokinetics - AUC0-90days of CT103A(1 year post CT103A infusion)
- Evaluation of lymphocyte subsets(1 year post CAR-T cell infusion)
- Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group(1 year post CT103A infusion)
- Pharmacokinetics of Selinexor(1 year post CT103A infusion)
- PD endpoints(1 year post CT103A infusion)
- Appraisal of life quality(1 year post CAR-T cell infusion)