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History of Changes for Study: NCT05028348
A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma
Latest version (submitted February 20, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 25, 2021 None (earliest Version on record)
2 February 16, 2022 Study Status, Arms and Interventions and Eligibility
3 July 26, 2022 Recruitment Status, Study Status, Contacts/Locations, Study Design and Oversight
4 February 20, 2023 Study Status, Arms and Interventions, Eligibility and Study Design
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Study NCT05028348
Submitted Date:  August 25, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: EMN29
Brief Title: A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma
Official Title: A Phase 3 Randomized, Open-label Trial of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2021
Overall Status: Not yet recruiting
Study Start: October 2021
Primary Completion: October 2022 [Anticipated]
Study Completion: October 2028 [Anticipated]
First Submitted: August 25, 2021
First Submitted that
Met QC Criteria:
August 25, 2021
First Posted: August 31, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
August 25, 2021
Last Update Posted: August 31, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Stichting European Myeloma Network
Responsible Party: Sponsor
Collaborators: Karyopharm Therapeutics Inc
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief 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).
Detailed Description:
Open or close this module Conditions
Conditions: Multiple Myeloma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 280 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Selinexor, pomalidomide and dexamethasone (SPd)

Selinexor will be given as an oral dose 60 mg (3 20 mg tablets) once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.

  • Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle.
  • Patients ≤75 years:

    o Dexamethasone will be given as an oral 40 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion.

  • Patients > 75 years:
    • Dexamethasone will be given as an oral 20 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion.
Drug: Selinexor
Selinexor will be given as an oral dose 60 mg (3 20 mg tablets) QW on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Names:
  • KPT-330
Drug: Pomalidomide
Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle.
Drug: 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.
Active Comparator: Elotuzumab, Pomalidomide and Dexamethasone (EloPd)

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 will be given as an oral 4 mg dose once a day (QD) on Days 1 to 21 of each 28-day cycle.
  • Patients ≤75 years:
    • Dexamethasone 28 mg PO + 8 mg IV on days of elotuzumab dosing
    • Dexamethasone 40 mg PO on non-elotuzumab days (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion.
  • Patients >75 years:
    • Dexamethasone 8 mg PO + 8 mg IV on days of elotuzumab dosing
    • Dexamethasone 20 mg PO on non-elotuzumab dosing weeks (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion.
Drug: 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.
Drug: Pomalidomide
Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle.
Drug: 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Progression-free survival (PFS)
[ Time Frame: from randomization to the date of disease progression or death (approximately up to 5 years) ]

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.
Secondary Outcome Measures:
1. Overall Response Rate (ORR)
[ Time Frame: from screening until end of treatment/progressive disease (approximately up to 2 years) ]

defined as any response ≥PR (i.e., PR [partial response], VGPR [very good partial response], CR ([complete response], or sCR [stringent complete response])
2. Overall survival (OS)
[ Time Frame: From randomization until death from any cause (up to 3 years after end of treatment) ]

Overall Survival
3. Duration of response
[ Time Frame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years ]

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.
4. Time to response
[ Time Frame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years ]

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)
5. Progression-free survival on the next line of therapy (PFS2)
[ Time Frame: the time from randomization to progression on the next line of treatment or death, whichever comes first., assessed up to approx. 5 years ]

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.
6. 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
[ Time Frame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (up to 2 years) ]

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.
7. Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score and the difference between-treatment arms
[ Time Frame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years) ]

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.
8. EQ-5D-5L health utility values and the difference between-treatment arms
[ Time Frame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years) ]

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"
9. safety and tolerability of SPd versus EloPd in patients with RRMM
[ Time Frame: continuously from screening untill 30 days after last study treatment. (approximately up to 2 years) ]

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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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 electrophoresis (SPEP) or, for immunoglobulin (Ig) A or D myeloma, by quantitative serum IgA or IgD levels
    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 regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 regimen.
  3. Patients must have prior therapy which must include and anti-CD3 mAb, and ≥2 consecutive cycles of the following agents given alone or in combinations: lenalidomide, proteasome inhibitor.
  4. Patients must have prior therapy with anti-CD38 mAb in one of the following ways:
    1. Received anti-CD38 mAb as their immediate last treatment prior to study entry (50% of patients)
    2. Received prior anti-CD38 mAb other than in immediate last treatment prior to study entry (50% of patients)
  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 following approval from the Medical Monitor.
  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. 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.
  11. Age ≥18 years at the time of signing informed consent.
  12. Written informed consent signed in accordance with federal, local, and institutional guidelines.
  13. 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.

Exclusion Criteria:

  1. Smoldering MM.
  2. Plasma cell leukemia.
  3. Documented active systemic amyloid light chain amyloidosis.
  4. Active central nervous system MM.
  5. Prior treatment with a selective inhibitor of nuclear export (SINE) compound, including selinexor.
  6. Prior treatment with pomalidomide and/or elotuzumab.
  7. Any concurrent medical condition or disease that is likely to interfere with study procedures.
  8. 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.
  9. Known intolerance, hypersensitivity, or contraindication to any of the study treatments.
  10. 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.
  11. Prior autologous stem cell transplantation <60 days or allogeneic stem cell transplantation <4 months prior to C1D1.
  12. Major surgery within 4 weeks prior to C1D1.
  13. Active graft versus host disease after allogeneic stem cell transplantation.
  14. Pregnant or breastfeeding females.
  15. In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight.
  16. 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 ECG abnormalities.
    3. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
  17. 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.
  18. 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.
  19. Contraindication to any of the required concomitant drugs or supportive treatments.
  20. Patients unwilling or unable to comply with the protocol.
Open or close this module Contacts/Locations
Central Contact Person: European Myeloma Network (EMN)
Telephone: +31 107033123
Email: chiara.pautasso@emnitaly.org
Locations: 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, France
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, Germany
Greece
Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
Athens, Greece
General Hospital of Athens"Euaggelismos"
Athens, Greece
St Savvas Cancer Hospital
Athens, Greece
University General Hospital of Patras
Patras, Greece
Theagenion Cancer Hospital
Thessaloníki, Greece
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, 50134
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, 28100
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, 10126
Azienda Ospedaliera Universitaria di Udine
Udine, Italy
Netherlands
Erasmus MC
Rotterdam, Netherlands
Spain
Hospital Clinic I Provincial de Barcelona
Barcelona, Spain
ICO Hospitalet
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, Spain
Open or close this module IPDSharing
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Open or close this module References
Citations:
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