Clinical trial NCT05201118: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Extramedullary Multiple Myeloma
Keywords: CT103A
Selinexor
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing IASO Biotechnology Co., Ltd.
First posted: 2022-01-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:

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  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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 1 year post CT103A infusion
measure: Objective response rate (ORR)
timeFrame: 1 year post CT103A infusion
measure: Duration of response (DOR) after administration
timeFrame: 1 year post CT103A infusion
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 1 year post CT103A infusion
measure: Minimal Residual Disease (MRD) efficacy evaluation
timeFrame: 1 year post CT103A infusion
measure: Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
timeFrame: 1 year post CT103A infusion
measure: Pharmacokinetics - Cmax of CT103A
timeFrame: 1 year post CT103A infusion
measure: Pharmacokinetics - Tmax of CT103A
timeFrame: 1 year post CT103A infusion
measure: Pharmacokinetics - AUC0-28days of CT103A
timeFrame: 1 year post CT103A infusion
measure: Pharmacokinetics - AUC0-90days of CT103A
timeFrame: 1 year post CT103A infusion
measure: Pharmacokinetics of Selinexor
timeFrame: 1 year post CT103A infusion
measure: PD endpoints
timeFrame: 1 year post CT103A infusion
measure: Health-related quality of life assessment
timeFrame: 1 year post CT103A infusion
measure: Appraisal of life quality
timeFrame: 1 year post CAR-T cell infusion
measure: Evaluation of lymphocyte subsets
timeFrame: 1 year post CAR-T cell infusion
measure: Concentration of immunoglobulins
timeFrame: 1 year post CAR-T cell infusion
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hu Bei
Study officials:
affiliation: Tongji Hospital
name: Chunrui Li
role: PRINCIPAL_INVESTIGATOR
References: