- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
Intervention / Treatment
- Procedure: Biospecimen Collection
- Procedure: Magnetic Resonance Imaging
- Procedure: Computed Tomography
- Biological: Daratumumab
- Procedure: Positron Emission Tomography
- Drug: Lenalidomide
- Drug: Dexamethasone
- Drug: Selinexor
- Drug: Bortezomib
- Drug: Daratumumab and Hyaluronidase-fihj
- Procedure: Bone Marrow Biopsy
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.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (Dara-SVD): Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) or daratumumab intravenously (IV) 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 biopsy and collection of blood samples during screening and at the end of treatment.
ARM II (Dara-RVD): Patients receive daratumumab and hyaluronidase-fihj SC or daratumumab IV 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. Patients also undergo PET, MRI, or CT, and bone marrow biopsy and collection of blood samples during screening and at the end of treatment.
After completion of study treatment, patients are followed up at 6 months and 1 and 2 years.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Laguna Hills, California, United States, 92653
- Recruiting
- UCI Health Laguna Hills
-
Principal Investigator:
- Lisa X. Lee
-
Contact:
- Site Public Contact
- Phone Number: 877-827-8839
- Email: ucstudy@uci.edu
-
Orange, California, United States, 92868
- Recruiting
- UC Irvine Health/Chao Family Comprehensive Cancer Center
-
Principal Investigator:
- Lisa X. Lee
-
Contact:
- Site Public Contact
- Phone Number: 877-827-8839
- Email: ucstudy@uci.edu
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
- Recruiting
- Yale University
-
Contact:
- Site Public Contact
- Phone Number: 203-785-5702
- Email: canceranswers@yale.edu
-
Principal Investigator:
- Natalia Neparidze
-
New Haven, Connecticut, United States, 06520
- Recruiting
- Yale University Cancer Center LAO
-
Contact:
- Natalia Neparidze
- Phone Number: 203-785-4144
- Email: natalia.neparidze@yale.edu
-
Principal Investigator:
- Natalia Neparidze
-
North Haven, Connecticut, United States, 06473
- Recruiting
- Yale-New Haven Hospital North Haven Medical Center
-
Contact:
- Site Public Contact
- Phone Number: 203-785-5702
- Email: canceranswers@yale.edu
-
Principal Investigator:
- Natalia Neparidze
-
Waterford, Connecticut, United States, 06385
- Recruiting
- Smilow Cancer Hospital Care Center - Waterford
-
Contact:
- Site Public Contact
- Phone Number: 203-785-5702
- Email: canceranswers@yale.edu
-
Principal Investigator:
- Natalia Neparidze
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Presence of newly diagnosed (dx) MM as defined by standard International Myeloma working group (IMWG).
- 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 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 evidence of progression.
- 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 2 negative pregnancy tests before initiating lenalidomide. The first test should be performed within 10-14 days and within 24 hours prior to prescribing lenalidomide and must either commit to continued 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 are in urgent need for MM therapy (such as in the setting of acute kidney injury, or high disease burden concerning for impending organ failure) may begin study treatment immediately after receiving one cycle of bortezomib combination (e.g. bortezomib-dexamethasone or cyclophosphamide-bortezomib-dexamethasone) or one course of pulse dose dexamethasone 20-40mg once daily for four days. No washout period is required.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (Dara-SVD)
Patients receive daratumumab and hyaluronidase-fihj SC or daratumumab IV 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 biopsy and collection of blood samples during screening and at the end of treatment.
|
Undergo collection of blood samples
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Given IV
Other Names:
Undergo PET
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given SC
Other Names:
Given SC
Other Names:
Undergo bone marrow biopsy
Other Names:
|
Active Comparator: Arm II (Dara-RVD)
Patients receive daratumumab and hyaluronidase-fihj SC or daratumumab IV 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 biopsy and collection of blood samples during screening and at the end of treatment.
|
Undergo collection of blood samples
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Given IV
Other Names:
Undergo PET
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given SC
Other Names:
Given SC
Other Names:
Undergo bone marrow biopsy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Deep clinical response
Time Frame: Up to the end of cycle 4 (each cycle = 28 days)
|
Defined as complete response (CR) + stringent CR.
|
Up to the end of cycle 4 (each cycle = 28 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimal residual disease-negativity (10^-5)
Time Frame: Up to end of cycle 4 (each cycle = 28 days)
|
Will be assessed by next generation flow cytometry.
|
Up to end of cycle 4 (each cycle = 28 days)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ribonucleic acid (RNA) and cell free deoxyribonucleic acid (DNA) sequencing
Time Frame: Baseline up to end of cycle 4 (each cycle = 28 days)
|
Will compare pre- and post-treatment RNA and cell free DNA sequencing data to identify unique differential signature correlated with deep responses among subjects treated with selinexor-daratumumab-velcade-dexamethasone regimen.
Will use cox proportional hazard models to identify a gene signature predictive of response to selinexor.
|
Baseline up to end of cycle 4 (each cycle = 28 days)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natalia Neparidze, Yale University Cancer Center LAO
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dermatologic Agents
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Lenalidomide
- Daratumumab
- Bortezomib
- Antibodies, Monoclonal
- Ichthammol
Other Study ID Numbers
- NCI-2023-07073 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- UM1CA186689 (U.S. NIH Grant/Contract)
- P30CA016359 (U.S. NIH Grant/Contract)
- 10612 (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on Biospecimen Collection
-
LLS PedAL Initiative, LLCNational Cancer Institute (NCI); Children's Oncology GroupRecruitingAcute Myeloid Leukemia | Juvenile Myelomonocytic Leukemia | Acute Lymphoblastic Leukemia | Myelodysplastic Syndrome | Myeloid Leukemia Associated With Down Syndrome | Mixed Phenotype Acute Leukemia | Acute Myeloid Leukemia Post Cytotoxic Therapy | Myelodysplastic Syndrome Post Cytotoxic TherapyUnited States, Canada, Australia, Puerto Rico, New Zealand
-
Thomas Jefferson UniversityNational Cancer Institute (NCI)Active, not recruiting
-
Mayo ClinicRecruitingMetastatic Breast Cancer | HER2-negative Breast Cancer | Hormone-receptor-positive Breast CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8United States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingBreast Adenocarcinoma | HER2-Positive Breast CarcinomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingAnatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC v8 | Prognostic Stage III Breast Cancer AJCC v8 | Prognostic Stage IIIA Breast Cancer AJCC v8 | Prognostic Stage IIIB Breast... and other conditionsUnited States, Puerto Rico
-
Ohio State University Comprehensive Cancer CenterGuardant Health, Inc.RecruitingColorectal CarcinomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Recruiting
-
Mayo ClinicRecruitingEarly Stage Breast Carcinoma | Chemotherapy-Related Nausea and/or VomitingUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruiting