NCT06169215

Comparing the Combination of Selinexor-Daratumumab-Velcade-Dexamethasone (Dara-SVD) With the Usual Treatment (Dara-RVD) for High-Risk Newly Diagnosed Multiple Myeloma

A Randomized Phase 2 Study of Daratumumab-Selinexor-Velcade-Dexamethasone (Dara-SVD) for High-Risk Newly Diagnosed Multiple Myeloma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the combination of selinexor, daratumumab and hyaluronidase-fihj (daratumumab), velcade (bortezomib), and dexamethasone (Dara-SVD) to the usual treatment of daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVD) in treating patients with high-risk newly diagnosed multiple myeloma. Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may keep cancer cells from growing and may kill them. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Bortezomib blocks several molecular pathways in a cell and may cause cancer cells to die. It is a type of proteasome inhibitor and a type of dipeptidyl boronic acid. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. The drugs daratumumab, lenalidomide, bortezomib, dexamethasone and selinexor are already approved by the Food and Drug Administration for use in myeloma. But selinexor is not used until myeloma comes back (relapses) after initial treatment. Giving selinexor in the initial treatment may be a superior type of treatment for patients with high-risk newly diagnosed multiple myeloma.

Detailed description

PRIMARY OBJECTIVE: I. To compare deep response (complete response \[CR\] + stringent CR \[sCR\]) by the end of induction cycle 4 in newly diagnosed high-risk multiple myeloma patients (HR NDxMM), in both study arms. SECONDARY OBJECTIVES: I. To assess the minimal residual disease (MRD)-negativity (10\^-5). II. To assess overall response rate (ORR), very good partial response (VGPR), and partial response (PR). III. To assess progression-free survival (PFS) and duration of response (DOR). CORRELATIVE OBJECTIVE: I. To identify differential gene expression signature that predicts response to selinexor through ribonucleic acid sequencing (RNAseq) and cell-free deoxyribonucleic acid (cfDNA) studies. EXPLORATORY THROMBOEMBOLISM RISK OBJECTIVES: I. To estimate cumulative incidence of venous and arterial thromboembolic events. II. To calculate IMPEDE and SAVED risk scores at baseline and at time of venous thromboembolic event. III. To describe thromboprophylaxis strategies on treatment and venous and arterial thromboembolic events. IV. To estimate incidence of clinically significant (major) bleeding events and assess association with thromboprophylaxis strategy. V. To assess the association of venous and arterial thromboembolic events with PFS and all-cause mortality. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (Dara-SVD): Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, \& 22 for cycles 1-2, then days 1 \& 15 for cycles 3-4, and selinexor orally (PO), bortezomib SC, and dexamethasone PO on days 1, 8, 15, \& 22 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET), magnetic resonance imaging (MRI), or computed tomography (CT), and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study. ARM II (Dara-RVD): Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, \& 22 for cycles 1-2, then days 1 \& 15 for cycles 3-4, lenalidomide PO once daily (QD) on days 1-21 of each cycle, and bortezomib SC and dexamethasone PO on days 1, 8, 15, \& 22 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET, MRI, or CT, and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study. After completion of study treatment, patients are followed up at 6 months and 1 and 2 years.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood and urine samples
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Bortezomib	Given SC
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Daratumumab and Recombinant Human Hyaluronidase	Given SC
DRUG	Dexamethasone	Given PO
DRUG	Lenalidomide	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET
DRUG	Selinexor	Given PO

Timeline

• Start date: 2024-07-23
• Primary completion: 2026-09-30
• Completion: 2026-09-30
• First posted: 2023-12-13
• Last updated: 2026-04-13

Locations

27 sites across 1 country: United States

Regulatory

• FDA-regulated drug study