Hematological malignancy relapsed and refractory multiple myeloma
Conditions
Interventions
Please refer to tables 2 and 3 in the synopsis.
Sponsors
Stichting European Myeloma Network (EMN)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: There is no difference in the patient population enrolled in Part 1 or Part 2 of the study. 1. Relapsed or refractory MM per IMWG criteria with measurable disease as defined by at least 1 of the following: a. 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. b. Urinary M-protein excretion >=200 mg/24 hours. c. 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 >=2 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 immediate last line of therapy prior to study entry (Before protocol version 2.0 patients with any prior therapy with an anti-CD38 mAb were eligible for the study.) 5. Eastern Cooperative Oncology Group (ECOG) performance status 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 10^9/L, hemoglobin >=8.5 g/dL, and platelet count >=100 x 10^9/L (patients for whom =75 x 109/L (patients for whom >=50% of bone marrow nucleated cells are plasma cells) a. 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., romiplostim, or eltrombopag) must have a 2-week interval between growth factor support and the Screening assessments. b. 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 In
Exclusion criteria
Exclusion criteria: There is no difference in the patient population enrolled in Part 1 or Part 2 of the study. This trial will enroll patients who meet all of the inclusion criteria and none of the exclusion criteria. 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: a. a selective inhibitor of nuclear export (SINE) compound, including selinexor. b. pomalidomide 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) 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 or inability to tolerate any of the required concomitant drugs such as dual antiemetics (Section 10.1.1 ), or supportive treatments. 19. Patients unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: PFS, defined as time 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
| Measure | Time frame |
|---|---|
| Key Secondary Efficacy Endpoints • OOR, defined as any response >= PR (i.e., PR [partial response], VGPR [very good partial response], CR ([complete response], or sCR [stringent complete response]) • Overall survival (OS) Additional Secondary Efficacy Endpoints • Clinical benefit rate (CBR), defined as response >=minimal response (MR) • Duration of response (DOR) • Time to next treatment (TNT) • Time to initial response (TTR) • Time to best response (TTBR) • Time to progression after first post-SPd/EloPd treatment or death (PFS2) Safety and tolerability of study treatment will be evaluated based on AE reports, vital signs, clinical laboratory results, electrocardiogram (ECG) and physical examination findings, by means of the occurrence, nature, and severity of AEs as categorized by the CTCAE v5.0. Patient-reported quality of life (QoL, as measured by the European Organisation for Research and Treatment of Cancer-Quality of Life (EORTC QLQ C30), EORTC-QLQ-MY20, and EQ-5D-5L instruments.. Selinexor and pomalidomide PK parameters, estimations of maximum plasma concentration, area under the concentration versus time curve (AUC), and apparent clearance, if feasible. | — |
Countries
Netherlands
Outcome results
None listed