Clinical trial NCT05028348: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Karyopharm Therapeutics Inc
First posted: 2021-08-31
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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 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-CD38 mAb as part of their immedicate last treatment prior to study entry (Before protocol version2.0, patient with any prior therapy with an anti-CD38 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: from randomization to the date of disease progression or death (approximately up to 5 years)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: from screening until end of treatment/progressive disease (approximately up to 2 years)
measure: Overall survival (OS)
timeFrame: From randomization until death from any cause (up to 3 years after end of treatment)
measure: Duration of response
timeFrame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years
measure: Time to response
timeFrame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years
measure: Progression-free survival on the next line of therapy (PFS2)
timeFrame: the time from randomization to progression on the next line of treatment or death, whichever comes first., assessed up to approx. 5 years
measure: 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
timeFrame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (up to 2 years)
measure: Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score and the difference between-treatment arms
timeFrame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years)
measure: EQ-5D-5L health utility values and the difference between-treatment arms
timeFrame: screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment (approximately up to 2 years)
measure: safety and tolerability of SPd versus EloPd in patients with RRMM
timeFrame: continuously from screening untill 30 days after last study treatment. (approximately up to 2 years)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Fresno
country: United States
facility: University of California, San Francisco
state: California
city: Irvine
country: United States
facility: Kaiser Permanente Southern California
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology Medical Group
state: California
city: West Hollywood
country: United States
facility: Berenson Oncology
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Fort Collins
country: United States
facility: UCHealth Cancer Center - Harmony Campus
state: Colorado
city: Delray Beach
country: United States
facility: Baptist Health South Florida
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Hollywood
country: United States
facility: Millennium Oncology Research Clinic
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists Panhandle
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Honolulu
country: United States
facility: Hawaii Cancer Care
state: Hawaii
city: Sioux City
country: United States
facility: June E. Nylen Cancer Center
state: Iowa
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Hospital
state: Louisiana
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland
state: Maryland
city: Grosse Pointe Woods
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: Lincoln
country: United States
facility: Nebraska Hematology - Oncology, P.C.
state: Nebraska
city: Reno
country: United States
facility: Cancer Care Specialists
state: Nevada
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Charlotte
country: United States
facility: Novant Health Cancer Institute
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute-Forsyth Medical Center
state: North Carolina
city: West Reading
country: United States
facility: Reading Hospital - McGlinn Cancer Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina. Hollings Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Cancer Center
state: South Carolina
city: El Paso
country: United States
facility: Renovatio Clinical Research
state: Texas
city: Houston
country: United States
facility: Millennium Research & Clinical Development
state: Texas
city: Lille
country: France
facility: CHRU Hôpital Claude Huriez
city: Nantes
country: France
facility: CHRU Hôtel Dieu
city: Paris
country: France
facility: CHU Hôpital Saint Antoine
city: Paris
country: France
facility: La Pitié
city: Paris
country: France
facility: Paris Necker
city: Poitiers
country: France
facility: CHU Poitiers - Pôle régional de Cancérologie
city: Toulouse
country: France
facility: Pôle IUCT Oncopole CHU
city: Bonn
country: Germany
facility: Johanniter Krankenhaus Bonn
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Düsseldorf
country: Germany
facility: Marien Hospital Dusseldorf
city: Greifswald
country: Germany
facility: University Medicine Greifswald, Medical Clinic and Polyclinic for Internal Medicine
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg - Eppendorf
city: Hanover
country: Germany
facility: KRH Klinikum Siloah
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg
city: Köln
country: Germany
facility: University Hospital of Cologne
city: München
country: Germany
facility: Red Cross Hospital Munich
city: Münster
country: Germany
facility: University Hospital of Münster
city: Würzburg
country: Germany
facility: University Hospital of Würzburg
city: Athens
country: Greece
facility: Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
city: Athens
country: Greece
facility: General Hospital of Athens"Evangelismos"
city: Athens
country: Greece
facility: St Savvas Cancer Hospital
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: Theagenion Cancer Hospital
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi Di Ancona
city: Bergamo
country: Italy
facility: A.O. Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Bologna
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia - Ematologia
city: Cagliari
country: Italy
facility: Ospedale Oncologico 'A. Businco'
city: Catania
country: Italy
facility: Aou Policlinico Rodolico San Marco
city: Firenze
country: Italy
facility: A.O.U. Careggi
city: Genova
country: Italy
facility: A.O.U. Policlinico S. Martino - Ematologia
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano. ASST Ovest Milanese
city: Meldola
country: Italy
facility: Hospital IRST
city: Messina
country: Italy
facility: A.O.U. Policlinico 'G. Martino'
city: Messina
country: Italy
facility: Azienda Ospedaliera Papardo
city: Milano
country: Italy
facility: ASST Santi Paolo e Carlo. SC Ematologia
city: Milano
country: Italy
facility: European Institute of Oncology, Haematology Division and Department
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità di Novara
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
city: Pescara
country: Italy
facility: Ospetale Santo Spirito
city: Ravenna
country: Italy
facility: UO Ematologia, Ospedale Santa Maria Delle Croci, AUSL Romagna
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Terni
country: Italy
facility: A.O. S. Maria
city: Terni
country: Italy
facility: SC Oncoematologia AO S. Maria di Terni
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U
city: Udine
country: Italy
facility: Azienda Ospedaliera Universitaria di Udine
city: Breda
country: Netherlands
facility: Amphia ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala D Oncolocia Hospitalet - Hospital Duran i Reynals
city: Gijón
country: Spain
facility: Hospital de Cabueñes
city: Girona
country: Spain
facility: Institut Català D'Oncologia - Hospital Dr. Josep Trueta
city: León
country: Spain
facility: Complejo Asistencial Universitario de Leon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Murcia
country: Spain
facility: H. General Universitario Morales Meseguer
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra (CUN)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: H. Universitario Marqués de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
city: Valencia
country: Spain
facility: H.U. La Fe
Study officials:
References: