Comparing the Combination of Selinexor-Daratumumab-Velcade-Dexamethasone (Dara-SVD) With the Usual Treatment (Dara-RVD) for High-Risk Newly Diagnosed Multiple Myeloma
NCT ID: NCT06169215
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
70 participants
INTERVENTIONAL
2024-07-23
2026-09-30
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (Dara-SVD)
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, and selinexor 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 PET, MRI, or CT, and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study.
Biospecimen Collection
Undergo collection of blood and urine samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Bortezomib
Given SC
Computed Tomography
Undergo CT
Daratumumab and Recombinant Human Hyaluronidase
Given SC
Dexamethasone
Given PO
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET
Selinexor
Given PO
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 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. Patients also undergo PET, MRI, or CT, and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study.
Biospecimen Collection
Undergo collection of blood and urine samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Bortezomib
Given SC
Computed Tomography
Undergo CT
Daratumumab and Recombinant Human Hyaluronidase
Given SC
Dexamethasone
Given PO
Lenalidomide
Given PO
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET
Interventions
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Biospecimen Collection
Undergo collection of blood and urine samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Bortezomib
Given SC
Computed Tomography
Undergo CT
Daratumumab and Recombinant Human Hyaluronidase
Given SC
Dexamethasone
Given PO
Lenalidomide
Given PO
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET
Selinexor
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Presence of high risk cytogenetics using fluorescent in situ hybridization (FISH) \[del(17p), t(4;14), t(14;16), t(14;20), chromosome 1 abnormalities, MYC translocation, tetrasomies, complex karyotype, high lactate dehydrogenase (LDH), or extramedullary MM.
* Patients are allowed to have received one cycle of bortezomib-based doublet or triplet therapy. For instance, if a newly diagnosed patient with MM is in need of urgent therapy, they may be enrolled after having received one cycle of bortezomib, cyclophosphamide, dexamethasone.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).
* Absolute neutrophil count ≥ 1,000/mcL (\> 500 if bone marrow \[BM\] clonal plasma cell involvement greater than 50%).
* Platelets ≥ 100,000/mcL (\> 50,000 if BM clonal plasma cell involvement greater than 50%).
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (with the exception of patients with Gilbert's syndrome who have a high baseline bilirubin).
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 × institutional ULN.
* Glomerular filtration rate (GFR) ≥ 30 mL/min.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with treated brain involvement are eligible if follow-up brain imaging performed within 10 days after central nervous system (CNS)-directed therapy shows no.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
* The effects of selinexor (KPT-330) on the developing human fetus are unknown. For this reason and because selective nuclear export inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men with partners of women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men (with partners of women of childbearing potential) treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study treatment administration. Adequate contraception should continue for 7 months for females and for 4 months for males after completion of the study treatment.
* Female of childbearing potential (FCBP) must have a negative pregnancy test during screening. They must either commit to continue abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before therapy, while taking lenalidomide, during dose interruptions, and for 7 months after study treatment. If menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her menstrual bleeding. Lenalidomide treatment must be discontinued during this evaluation.
* Men who are sexually active with FCBP must agree to use a latex or synthetic condom while taking lenalidomide, during dose interruptions and for up to 4 weeks after discontinuing lenalidomide, even if they have undergone a successful vasectomy. Male patients taking lenalidomide must abstain from donating blood, semen, or sperm during study participation and for at least 4 weeks after discontinuation from lenalidomide.
* Patients who are randomized to receive lenalidomide need to register into the mandatory Risk Evaluation and Mitigation Strategies (REMS) program and be willing and able to comply with the requirements of REMS.
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor (KPT-330) or other agents used in study.
* Concomitant medications: Supportive care therapies such as bone directed therapies (zoledronic acid, denosumab), intravenous immunoglobulin therapy (IVIG) and anti-viral agents are allowed and recommended as per standard of care (SOC). Strong CYP3A4 inhibitors and strong CYP3A4 inducers are prohibited, due to their respective increase or decrease in bortezomib exposure. If strong CYP3A4 inhibitors cannot be avoided, then patients will be monitored for signs of bortezomib toxicity and a dose reduction of bortezomib will be considered.
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
* Pregnant women are excluded because this study involves an investigational drug that may cause genotoxic, teratogenic, and mutagenic effects on the developing fetus and newborn and drugs that have known genotoxic, teratogenic, or abortifacient effect.
* Because there is potential risk for adverse events in nursing infants secondary to treatment of the mother with the drugs used in this study, breastfeeding is not allowed during treatment for all drugs and for 2 months after last dose of bortezomib and 1 week after the last dose of selinexor.
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Natalia Neparidze
Role: PRINCIPAL_INVESTIGATOR
Yale University Cancer Center LAO
Locations
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UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UCI Health Laguna Hills
Laguna Hills, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
NYU Langone Hospital - Brooklyn
Brooklyn, New York, United States
NYU Langone Hospital - Long Island
Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Countries
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Other Identifiers
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NCI-2023-07073
Identifier Type: REGISTRY
Identifier Source: secondary_id
10612
Identifier Type: OTHER
Identifier Source: secondary_id
10612
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2023-07073
Identifier Type: -
Identifier Source: org_study_id