RECRUITING

A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

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)

Quick Facts

Study Start:2022-04-19

Study Completion:2029-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05028348

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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.	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.

Inclusion Criteria

Exclusion 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.
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.

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.

Contacts and Locations

Study Contact

European Myeloma Network (EMN)

CONTACT

+31 107033123

chiara.pautasso@emnitaly.org

Study Locations (Sites)

The University of Arizona Cancer Center

Tucson, Arizona, 85724

United States

California Cancer Associates for Research and Excellence

Encinitas, California, 92024

United States

University of California, San Francisco

Fresno, California, 93701

United States

Kaiser Permanente Southern California

Irvine, California, 92618

United States

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017

United States

Berenson Oncology

West Hollywood, California, 90069

United States

The Oncology Institute of Hope and Innovation

Whittier, California, 90602

United States

UCHealth Cancer Center - Harmony Campus

Fort Collins, Colorado, 80528

United States

Baptist Health South Florida

Delray Beach, Florida, 33486

United States

Florida Cancer Specialists South

Fort Myers, Florida, 33901

United States

Millennium Oncology Research Clinic

Hollywood, Florida, 33024

United States

Florida Cancer Specialists North

Saint Petersburg, Florida, 33705

United States

Florida Cancer Specialists Panhandle

Tallahassee, Florida, 32308

United States

Florida Cancer Specialists East

West Palm Beach, Florida, 33401

United States

Hawaii Cancer Care

Honolulu, Hawaii, 96813

United States

June E. Nylen Cancer Center

Sioux City, Iowa, 51101

United States

Our Lady of the Lake Hospital

Baton Rouge, Louisiana, 70808

United States

Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809

United States

American Oncology Partners of Maryland

Bethesda, Maryland, 20817

United States

Ascension St. John Hospital

Grosse Pointe Woods, Michigan, 48236

United States

Nebraska Hematology - Oncology, P.C.

Lincoln, Nebraska, 68506

United States

Cancer Care Specialists

Reno, Nevada, 89511

United States

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103-1461

United States

Novant Health Cancer Institute

Charlotte, North Carolina, 28204

United States

East Carolina University

Greenville, North Carolina, 27834

United States

Novant Health Cancer Institute-Forsyth Medical Center

Winston-Salem, North Carolina, 27103

United States

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, 19611

United States

Medical University of South Carolina. Hollings Cancer Center

Charleston, South Carolina, 29425

United States

Gibbs Cancer Center

Spartanburg, South Carolina, 29303

United States

Renovatio Clinical Research

El Paso, Texas, 79915

United States

Millennium Research & Clinical Development

Houston, Texas, 77090

United States

Collaborators and Investigators

Sponsor: Stichting European Myeloma Network

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-04-19

Study Completion Date2029-03

Study Record Updates

Study Start Date2022-04-19

Study Completion Date2029-03

Terms related to this study

Additional Relevant MeSH Terms

Multiple Myeloma