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

NCT05201118 | Unknown Phase 1

• 1 other identifier: CAR CT103A SELINEXOR001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Extramedullary Multiple Myeloma

Keywords

CT103A; Selinexor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• Overall survival (OS)

  1 year post CT103A infusion

• Minimal Residual Disease (MRD) efficacy evaluation

  1 year post CT103A infusion

• Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group

  1 year post CT103A infusion

• Pharmacokinetics - Cmax of CT103A

  1 year post CT103A infusion

• Pharmacokinetics - Tmax of CT103A

  1 year post CT103A infusion

Study Arms (1)

CT103A combined with Selinexor

EXPERIMENTAL

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; Drug: CT103A

Interventions

Selinexor DRUG

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.

CT103A combined with Selinexor

CT103A DRUG

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).

CT103A combined with Selinexor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
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• 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.
• Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
• Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
• SpO2 \> 91%.
• 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.

You may not qualify if:

• 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.
• 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)
• Subjects participated in another interventional clinical study within 1 month before signing the informed consent (ICF).
• Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis.
• 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

Sponsors & Collaborators

• Chunrui Li: lead
• Nanjing IASO Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Related Publications (1)

• Keam SJ. Equecabtagene Autoleucel: First Approval. Mol Diagn Ther. 2023 Nov;27(6):781-787. doi: 10.1007/s40291-023-00673-y. Epub 2023 Sep 2.

  PMID: 37658205 DERIVED

MeSH Terms

Interventions

selinexor; CT103A chimeric antigen receptor

Study Officials

• Chunrui Li

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunrui Li

CONTACT

86-13647233185; cunrui5650@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 21, 2022
• Study Start: January 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: May 24, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)