Clinical trial NCT05900882: SVRd for the Treatment of Newly Diagnosed Multiple Myeloma Patients Presenting With Extramedullary Disease
Official title: An Open Label, Single Arm, Multi-Center Exploratory Study to Evaluate the Efficacy and Safety of SVRd for the Treatment of Newly Diagnosed Multiple Myeloma Patients Presenting With Extramedullary Disease.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: NDMM
Extramedullary disease
SVRd
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-06-13
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of SVRd in NDMM patients presenting with extramedullary disease.

Detailed description: Study Design:

This protocol corresponds to a multicenter, open-label, single arm, exploratory study designed to determine the safety of the combination of selinexor combined with VRd in NDMM patients presenting with EMD. The patients who respond to this combination treatment will undergo allogeneic hematopoietic stem cell transplantation or no ASCT and followed by consolidation and maintenance treatment.

All patients will receive 4 courses of SVRd induction therapy, each cycle of treatment will compromise 4 weeks of Selinexor 60mg QW treatment. Transplantation could be performed after 2 courses of VRd consolidation therapy. If not receive transplantation will give 4 cycles of SVRd consolidation therapy. Maintenance treatment will continued for a maximum of 2 years.

Study design allows 35 patients. Induction treatment will consist of Selinexor 60 mg/day orally on d1,8,15,22, Bortezomib 1.3mg/m2 intravenously on d1,8,15,22, Lenalidomide 25 mg/d ( the dose will be adjusted according to creatinine clearance), orally on days 1 to14, Dexamethasone 20 mg/day orally on d1-2, d8-9,d15-16,d22-23

Eligibility criteria: Inclusion Criteria:

1. Men and women aged with18-75 years old.
2. Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
3. Newly diagnosed patients presenting with extramedullary disease (EMD) including solely paraskeletal plasmacytoma, plasmacytoma of soft tissue and other special sites detected by physical exam and confirmed by CT/MRI/PET-CT and/or biopsy (≥2cm).
4. ANC≥1.0\*10\^9/L, HGB≥75\*10\^9/L, PLT≥50\*10\^9/L (≥50% of bone marrow nucleated cells are plasma cells).
5. Patients whose expecting survival time will be more than 3 months.
6. Without active infectious disease.
7. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and all patients agree to use two reliable methods of contraception for six months after their last dose of medication.
8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
9. Each patient must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

1. Patients who have HBV, HCV, and other acquired and congenital immunodeficiency diseases.
2. Patients who have grade 2 or higher of peripheral neuropathy or neuralgia according to the definition of NCI CTCAE version 4.0.
3. Plasma cell leukemia.
4. Serious thrombotic events.
5. Active, unstable cardiovascular dysfunction: a. symptomatic ischemia; b. Uncontrolled, clinically significant conduction abnormalities (except antiarrhythmic ventricular tachycardia), but patients with first-degree atrioventricular block or asymptomatic left anterior bundle/right fascicular block cannot be excluded. c. New York Heart Association (NYHA) Class III - IV or left ventricular ejection fraction (LVEF) \<40%; d. Myocardial infarction Within 3 months before C1D1.
6. Significant hepatic dysfunction (ALT and AST ≥ 3 times the upper limit of normal (ULN)).
7. Serum bilirubin≥1.5 × ULN.
8. creatinine clearance \<30 ml/min.
9. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma.
10. Previous major operation within 30 days before C1D1.
11. Patients who have epilepsy, dementia requiring medication, or other mental disorders who are unable to understand or adhere to the study protocol.
12. According to the study protocol or in the opinion of the investigator,serious physical or mental illness that is likely to interfere with the study procedures/results.
13. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
14. Current participation in another clinical trial.
15. Pregnant or lactating women.
16. Patients with other commodities that the investigators considered not suitable for the enrollment.

Primary outcomes:
measure: Number of Participants With Overall Response Rate (ORR)
timeFrame: End of induction treatment (4 cycles, each cycle is 28 days)
Secondary outcomes:
measure: Number of Participants With Complete Response Rate (CR)
timeFrame: End of induction treatment (4 cycles, each cycle is 28 days)
measure: Duration of Response (DOR)
timeFrame: 5 years
measure: Progression-Free Survival (PFS)
timeFrame: 5 years
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Number of adverse events
timeFrame: During of induction treatment (4 cycles, each cycle is 28 days)
Other outcomes:
Locations:
city: Changzhou
country: China
facility: Changzhou Second People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng First People's Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Lijuan Chen
role: STUDY_CHAIR
References: