Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

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.

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.

Selinexor

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

Chunrui Li

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.

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.

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.

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

The time from the start of CT103A treatment for the subjects to the first disease progression or death for any reason.

The percentage of subjects who achieved sCR、CR、VGPR、PR.

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

OS is measured from the date of the initial infusion of CT103A to the date of the participant's death.

MRD evaluation according to IMWG, including the proportion of subjects who achieved MRD negative and the duration of MRD negative.

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

The maximum transgene level at Cmax fo CT103A

The maximum transgene level at Tmax fo CT103A

Area under the curve of CT103A cells from time zero to Day 28 of CT103A

Area under the curve of CT103A cells from time zero to Day 90 of CT103A

The changes of concentration of Selinexor in peripheral blood will be assessed.

The concentration levels of CAR-T-related serum cytokines such as Ferritin and IL-6

HRQoL will be assessed by the European Organization for Cancer Research and Treatment Quality of Life Questionnaire (EORTC-QLQ-C30)

Appraisal of life quality of the subjects will be assessed by the Quality of Life Multiple Myeloma Module Questionnaire (QLQ-MY20)

Lymphocyte subsets will be assessed by FACS

The levels of Immunoglobulins in peripheral blood will be assessed to monitor changes at each time point

Nanjing IASO Biotechnology Co., Ltd.

Professor

Leukemia

Leukemia, Plasma Cell

Plasma Cell Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Dexamethasone

Melphalan

Cisplatin

Epirubicin

Lenalidomide

Bortezomib

Daratumumab

Dexamethasone acetate

BB 1101

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Pretrial induction chemotherapy (if required): bortezomib, cyclophosphamid, dexamethasone (VCD).

Induction Chemotherapy: Daratumumab, Carfilzomib,Lenalidomide, Dexamethasone, CisPlatin, epirubicin, Cyclophosphamide and Etoposide (Dara-KRd-PACE).

Autologous Stem Cell Transplant (ASCT) : Melphalan, ASCT.

Consolidation: Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone (Dara-KRd).

Maintenance: Daratumumab, Carfilzomib, and Dexamethasone (Dara-Kd).

Given by vein: days 1 and 8 of each Induction cycle; days 1 and 15 of each Consolidation cycle; and day 1of each Maintenance cycle.

Given by vein: days 1,2,8 and 9 of each Induction cycle; days 1, 2, 8, 9,15, and 16 of each Consolidation cycle; days 1, 2,15, and 16 of each Maintenance cycle.

Carfilzomib

Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.

Given by mouth or by vein: days 1, 8, 15, and 22 of each Induction cycle; days 1, 8, 15, and 22 of each Consolidation cycle; and days 1 and 15 of every cycle during Maintenance

Given by vein: days 1-4 of each Induction cycle

epirubicin

ASCT

given by subcutaneous injection: days 1, 4, 8, and 11 of pretrial induction chemotherapy

bortezomib

Chunyan Sun, MD

Jian Xu, MD

This study will assess whether the combination of daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with ASCT improves the outcome of patients with ultra high-risk, newly diagnosed multiple myeloma

Survival outcomes for patients with newly diagnosed multiple myeloma (MM) have improved substantially in the past decades, due to the introduction of novel therapeutic strategies. Unfortunately, patients with ultra-high-risk MM, including "double-hit" MM, extramedullary MM (EMM), and primary plasma cell leukemia (pPCL), have a significantly worse prognosis and benefit less from current therapeutic strategies. This study aims to investigate whether a treatment regimen combining daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with autologous stem cell transplantation (ASCT) can improve the survival outcomes of newly diagnosed, transplant-eligible, ultra high-risk multiple myeloma patients. In the study, participants will receive induction therapy with 2-4 cycles of Dara-KRd-PACE, followed by ASCT, 4 cycles of Dara-KRd consolidation, and then maintenance with 12 cycles of Dara-Kd.

Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma

Clinical Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma

2-year Progression-free survival of participants as determined by investigator assessment.

progression-free survival of participants as determined by investigator assessment.

overall survival of participants as determined by investigator assessment.

Overall response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

Minimal Residual Disease (MRD) negativity rate as assessed by next generation sequencing.

complete response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

graded according to the Common Terminology Criteria for Adverse Events v5

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in Patients With Relapsed/Refractory Extramedullary Multiple Myeloma	NCT05201118	Extramedullary ...	Selinexor CT103A	18 Years -	Tongji Hospital
Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma	NCT06140966	Multiple Myelom... Primary Plasma ... Extramedullary ...	Daratumumab Carfilzomib Lenalidomide Dexamethasone Cisplatin epirubicin Cyclophosphamid... Etoposide Melphalan ASCT bortezomib	18 Years - 70 Years	Wuhan Union Hospital, China

Spots Global Cancer Trial Database for extramedullary multiple myeloma