Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 3
Stichting European Myeloma Network (Voir sur ClinicalTrials)
avril 2022
mars 2029
29 octobre 2024
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).
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Necker-Enfants Malades | Frenzel | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Saint Antoine | Mohty | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHRU Hôpital Claude Huriez - Lille - France | Manier | Contact (sur clinicalTrials) | |||
| CHRU Hôtel Dieu - Nantes - France | Moreau | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHU Poitiers - Pôle régional de Cancérologie - Poitiers - France | Leleu | Contact (sur clinicalTrials) | |||
| La Pitié - Paris - France | Morel | Contact (sur clinicalTrials) | |||
| Pôle IUCT Oncopole CHU - Toulouse - France | Perrot | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.
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.