A Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in Patients With Relapsed/Refractory Extramedullary Multiple Myeloma

Phase 1

• Conditions: Extramedullary Multiple Myeloma
• Interventions: Drug: Selinexor; Drug: CT103A

• Registration Number: NCT05201118
• Lead Sponsor: Chunrui Li

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.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-20
• Study First Posted: 2022-01-21
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-17
• Last Update Posted: 2022-05-24
• Primary Completion: 2022-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

  7. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CT103A combined with Selinexor	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.
CT103A combined with Selinexor	CT103A	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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)
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.
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.
Pharmacokinetics - Cmax of CT103A	1 year post CT103A infusion	The maximum transgene level at Cmax fo CT103A
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
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
Evaluation of lymphocyte subsets	1 year post CAR-T cell infusion	Lymphocyte subsets will be assessed by FACS
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
Pharmacokinetics of Selinexor	1 year post CT103A infusion	The changes of concentration of Selinexor in peripheral blood will be assessed.
PD endpoints	1 year post CT103A infusion	The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6
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)

Trial Locations

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hu Bei, China