Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05028348
Other study ID # EMN29
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date April 19, 2022
Est. completion date March 2029

Study information

Verified date February 2023
Source European Myeloma Network
Contact European Myeloma Network (EMN)
Phone +31 107033123
Email chiara.pautasso@emnitaly.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase 3 randomized, open-label multicenter trial will compare the efficacy, safety and the impact on health-related quality of life (HR-QoL) of SPd versus EloPd in pomalidomide-naïve patients with MM who have received 1 to 4 prior anti-MM regimens and been treated with an immunomodulatory imide drug (IMiD), proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody (mAb).


Recruitment information / eligibility

Status Recruiting
Enrollment 222
Est. completion date March 2029
Est. primary completion date March 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Relapsed or refractory MM with measurable disease per IMWG guidelines as defined by at least 1 of the following: 1. Serum M-protein =0.5 g/dL (=5 g/L) by serum protein electrophoresis (SPEP) or, for immunoglobulin (Ig) A or D myeloma, by quantitative serum IgA or IgD levels = 0.5 g/dL. 2. Urinary M-protein excretion =200 mg/24 hours 3. Serum free light chain (FLC) =100 mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65) 2. Received at least 1 and no more than 4 prior anti-MM lines of therapy. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy. 3. Prior therapy that includes = consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination 4. Prior therapy with an anti-CD3 mAb as part of their immedicate last treatment prior to study entry (Before protocol version2.0, patient with any prior therapy with an anti-CD3 mAb were eligible for the study). 5. Eastern Cooperative Oncology Group (ECOG) performance status of =2. 6. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to Grade =1 by Cycle 1 Day 1 (C1D1). Patients with Grade 2 non-hematological toxicities may be included. 7. Adequate hepatic function within 28 days prior to C1D1: 1. Total bilirubin <2 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of <3 × ULN) 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × ULN 8. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of =15 mL/min (not requiring dialysis), calculated using the formula of Cockcroft and Gault or measured by 24-hour urine collection). 9. Adequate hematopoietic function within 7 days prior to C1D1 defined as absolute neutrophil count =1.5 x 109/L , hemoglobin =8.5 g/dL, and platelet count =100 x 109/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or =75 x 109/L (patients for whom =50% of bone marrow nucleated cells are plasma cells). 1. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study. 2. Patients must have: - At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and - At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study. 10. Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/mL. Patients with evidence of non-active HBV should be discussed with the Medical Monitor and should be monitored or receive prophylaxis at the discretion of the Investigator and study site institutional guidelines 11. Patients with a history of hepatitis C virus (HCV) are eligible if they have received adequate curative anti-HCV treatment and HCV viral load is below the limit of quantification. 12. Patients with a history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T cell counts =350 cells/µL, negative viral load, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year and should be on established antiretroviral therapy (ART) for at least 4 weeks. 13. Female patients of childbearing potential must have a negative serum pregnancy test within 10 to 14 days and a second test within 24 hours prior to the first dose of study treatment. Female patients of childbearing potential and fertile male patients who are sexually active must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment. 14. Age =18 years at the time of signing informed consent. 15. Written informed consent signed in accordance with federal, local, and institutional guidelines. 16. Patients must be able and willing to take enteric-coated aspirin according to clinical practice, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (international normalized ratio [INR] 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE) at the Investigator's discretion. For patient on warfarin, INR should be repeated as clinically indicated. Use of alternative anticoagulants, such as direct oral anticoagulants, may be considered per Investigator discretion. Exclusion Criteria: 1. Smoldering MM. 2. Plasma cell leukemia. 3. Documented active systemic amyloid light chain amyloidosis. 4. Any history of central nervous system MM. 5. Prior treatment with: 1. A selective inhibitor of nuclear export (SINE) compound, including selinexor 2. Pomalidomide and/or elotuzumab. 6. Any concurrent medical condition or disease that is likely to interfere with study procedures. 7. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable. 8. Known intolerance, hypersensitivity, or contraindication to any of the study treatments. 9. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy including investigational therapies and high dose dexamethasone (i.e., 40 mg daily for 4 days per week) =2 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study. 10. Prior autologous stem cell transplantation <60 days or allogeneic stem cell transplantation <4 months prior to C1D1. 11. Major surgery within 4 weeks prior to C1D1. 12. Active graft versus host disease after allogeneic stem cell transplantation. 13. Pregnant or breastfeeding females. 14. In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight. 15. Clinically significant cardiac disease, including: 1. Myocardial infarction within 6 months before C1D1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV). 2. Uncontrolled cardiac arrhythmia (CTCAE v. 5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities. 3. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec. 16. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment. 17. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent. 18. Contraindication to any of the required concomitant drugs or supportive treatments. 19. Patients unwilling or unable to comply with the protocol.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Selinexor
Selinexor will be given as an oral dose 40 mg (2 20 mg tablets) QW on Days 1, 8, 15, and 22 of each 28-day cycle.
Elotuzumab
Elotuzumab will be given IV 10 mg/kg on Days 1, 8, 15, and 22 of cycle 1 and 2 then 20 mg/kg on Day 1 of cycles =3 of each 28-day cycle.
Pomalidomide
Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle.
Dexamethasone Oral
Dexamethasone will be given as an oral 40 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Preferred dosing of dexamethasone is 40 mg QW for patients who are =75 years of age (20 mg QW for >75-year-old patients at the Investigator's discretion) before QW dosing of selinexor, however, it may be divided over 2 days at the Investigator's discretion.

Locations

Country Name City State
France CHRU Hôpital Claude Huriez Lille
France CHRU Hôtel Dieu Nantes
France CHU Hôpital Saint Antoine Paris
France La Pitié Paris
France Paris Necker Paris
France CHU Poitiers - Pôle régional de Cancérologie Poitiers
France Pôle IUCT Oncopole CHU Toulouse
Germany Universitätsklinikum Hamburg - Eppendorf Hamburg
Germany University Hospital of Heidelberg Heidelberg
Germany University Hospital of Cologne Köln
Germany University Hospital of Münster Münster
Germany University Hospital of Würzburg Würzburg
Greece Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens Athens
Greece General Hospital of Athens"Evangelismos" Athens
Greece St Savvas Cancer Hospital Athens
Greece University General Hospital of Patras Patras
Greece Theagenion Cancer Hospital Thessaloníki
Italy Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi Di Ancona Ancona
Italy A.O. Papa Giovanni XXIII Bergamo
Italy Bologna Bologna
Italy ASST Spedali Civili di Brescia - Ematologia Brescia
Italy Brescia Brescia
Italy Ospedale Oncologico 'A. Businco' Cagliari
Italy Az.Osp. Di Careggi_Dh ematologia Firenze
Italy A.O.U. Policlinico S. Martino - Ematologia Genova
Italy Hospital IRST Meldola
Italy A.O.U. Policlinico 'G. Martino' Messina
Italy A.O.U. Maggiore della Carità di Novara Novara
Italy Ospedale S. Eugenio Roma
Italy A.O. S. Maria Terni
Italy A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U Torino
Italy Azienda Ospedaliera Universitaria di Udine Udine
Netherlands Amphia ziekenhuis Breda
Netherlands Erasmus MC Rotterdam
Spain Hospital Clinic I Provincial de Barcelona Barcelona
Spain Institut Catala D Oncolocia Hospitalet - Hospital Duran i Reynals Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
Spain H. General Universitario Morales Meseguer Murcia
Spain Clínica Universidad de Navarra (CUN) Pamplona
Spain Hospital Universitario de Salamanca Salamanca
Spain H. Universitario Marqués de Valdecilla Santander
Spain Complejo Hospitalario Universitario de Santiago (CHUS) Santiago De Compostela
Spain H.U. La Fe Valencia
United States Hematology Oncology Clinic Baton Rouge Louisiana
United States American Oncology Partners of Maryland Bethesda Maryland
United States MD Anderson Cancer Center at Cooper Camden New Jersey
United States Medical University of South Carolina. Hollings Cancer Center Charleston South Carolina
United States UCHealth Cancer Center - Harmony Campus Fort Collins Colorado
United States Florida Cancer Specialists South Fort Myers Florida
United States University of California, San Francisco Fresno California
United States East Carolina University Greenville North Carolina
United States Ascension St. John Hospital Grosse Pointe Woods Michigan
United States Hawaii Cancer Care Honolulu Hawaii
United States Kaiser Permanente Southern California Irvine California
United States Nebraska Hematology - Oncology, P.C. Lincoln Nebraska
United States Los Angeles Hematology Oncology Medical Group Los Angeles California
United States Cancer Care Specialists Reno Nevada
United States Florida Cancer Specialists North Saint Petersburg Florida
United States June E. Nylen Cancer Center Sioux City Iowa
United States Gibbs Cancer Center Spartanburg South Carolina
United States Florida Cancer Specialists Panhandle Tallahassee Florida
United States Renovatio Clinical Research The Woodlands Texas
United States The University of Arizona Cancer Center Tucson Arizona
United States Berenson Oncology West Hollywood California
United States Florida Cancer Specialists East West Palm Beach Florida
United States Reading Hospital - McGlinn Cancer Institute West Reading Pennsylvania
United States The Oncology Institute of Hope and Innovation Whittier California
United States Novant Health Cancer Institute Winston-Salem North Carolina

Sponsors (2)

Lead Sponsor Collaborator
European Myeloma Network Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Italy,  Netherlands,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free survival (PFS) from date of randomization until the date of first confirmed progressive disease (PD), per IMWG response criteria, or death due to any cause, whichever occurs first. from randomization to the date of disease progression or death (approximately up to 5 years)
Secondary Overall Response Rate (ORR) defined as any response =PR (i.e., PR [partial response], VGPR [very good partial response], CR ([complete response], or sCR [stringent complete response]) from screening until end of treatment/progressive disease (approximately up to 2 years)
Secondary Overall survival (OS) Overall Survival From randomization until death from any cause (up to 3 years after end of treatment)
Secondary Duration of response Duration of response (PR or better), duration of CR, duration of sCR, and duration of minimal residual disease (MRD) -negative status, are calculated from the date of the initial documentation of a response (PR or better), or CR or better, or sCR, or MRD-negative status to the date of the first documented evidence of disease progression, as defined in the IMWG criteria, whichever occurs first. screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years
Secondary Time to response Time to response (PR or better), time to CR/sCR are defined as the time from randomization to date of initial response (or initial CR/sCR) screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years
Secondary Progression-free survival on the next line of therapy (PFS2) Progression-free survival on the next line of therapy (PFS2) is defined as the time from randomization to progression on the next line of treatment or death, whichever comes first. the time from randomization to progression on the next line of treatment or death, whichever comes first., assessed up to approx. 5 years
Secondary Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) score and the difference between-treatment arms The EORTC QLQ-C30 is a 30-item questionnaire containing both single and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/ Quality-of-Life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The scores ranges from 0-100, a high score for functional scales and for Global Health Status/QoL represent better functioning ability or Health-Related Quality-of-Life (HRQoL), whereas a high score for symptom scales and single items represents significant symptomatology. screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (up to 2 years)
Secondary Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score and the difference between-treatment arms The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in subjects with MY. The module comprises 20 questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side Effects of Treatment, Future Perspective, and Body Image. A high score for Disease Symptoms and Side Effects of Treatment represents a high level of symptomatology or problems, whereas a high score for Future Perspective and Body Image represents better outcomes. screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years)
Secondary EQ-5D-5L health utility values and the difference between-treatment arms The EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today" screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years)
Secondary safety and tolerability of SPd versus EloPd in patients with RRMM Safety and tolerability of study treatment will be evaluated based on occurrence, nature and severity of adverse events as categorized by the Common Terminology Criteria of Adverse Events (CTCAE) v5.0 continuously from screening untill 30 days after last study treatment. (approximately up to 2 years)
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1