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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Extramedullary Multiple Myeloma
• Intervention / Treatment: Drug: Selinexor; Drug: CT103A

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hu Bei
    • Wuhan, Hu Bei, China, 430000
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Selinexor; 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.; Drug: CT103A; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year post CT103A infusion
Objective response rate (ORR)	The percentage of subjects who achieved sCR、CR、VGPR、PR.	1 year post CT103A infusion
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	1 year post CT103A infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is measured from the date of the initial infusion of CT103A to the date of the participant's death.	1 year post CT103A infusion
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.	1 year post CT103A infusion
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	1 year post CT103A infusion
Pharmacokinetics - Cmax of CT103A	The maximum transgene level at Cmax fo CT103A	1 year post CT103A infusion
Pharmacokinetics - Tmax of CT103A	The maximum transgene level at Tmax fo CT103A	1 year post CT103A infusion
Pharmacokinetics - AUC0-28days of CT103A	Area under the curve of CT103A cells from time zero to Day 28 of CT103A	1 year post CT103A infusion
Pharmacokinetics - AUC0-90days of CT103A	Area under the curve of CT103A cells from time zero to Day 90 of CT103A	1 year post CT103A infusion
Pharmacokinetics of Selinexor	The changes of concentration of Selinexor in peripheral blood will be assessed.	1 year post CT103A infusion
PD endpoints	The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6	1 year post CT103A infusion
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)	1 year post CT103A infusion
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)	1 year post CAR-T cell infusion
Evaluation of lymphocyte subsets	Lymphocyte subsets will be assessed by FACS	1 year post CAR-T cell infusion
Concentration of immunoglobulins	The levels of Immunoglobulins in peripheral blood will be assessed to monitor changes at each time point	1 year post CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Chunrui Li
• Collaborators: Nanjing IASO Biotherapeutics Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Selinexor; CT103A
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CAR CT103A SELINEXOR001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No