Selinexor and Backbone Treatments of Multiple Myeloma Patients
Summary
This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are: * Arm 1: Selinexor + dexamethasone + pomalidomide (SPd); enrollment complete * Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete * Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete * Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd); enrollment complete * Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete * Arm 6: Selinexor + dexamethasone + carfilzomib (SKd); enrollment complete * Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM; enrollment complete * Arm 8: Selinexor + dexamethasone + ixazomib (SNd); enrollment complete * Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd); enrollment complete * Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd); enrollment complete * Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd); enrollment complete * Arm 12: Selinexor + dexamethasone + mezigdomide (SMd); actively recruiting Selinexor pharmacokinetics: * PK Run-in (Days 1-14): Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 \[SPVd\], Arm 6 \[SKd\], Arm 8 \[SNd\], Arm 9 \[SPEd\], Arm 10 \[SBd\], and Arm 11 \[SDPd\]) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor. This run-in period does not apply to Arm 12 (SMd).
Timeline
- Start
- 2015-10
- Primary completion
- 2027-04
- Completion
- 2027-04
Publications
- White D, Schiller GJ, Madan S, Lentzsch S, Chubar E, Lavi N, Van Domelen DR, Bentur OS, Baljevic M. Efficacy and safety of once weekly selinexor 40 mg versus 60 mg with pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Front Oncol. 2024 May 17;14:1352281. doi: 10.3389/fonc.2024.1352281. eCollection 2024.
- Schiller GJ, Lipe BC, Bahlis NJ, Tuchman SA, Bensinger WI, Sutherland HJ, Lentzsch S, Baljevic M, White D, Kotb R, Chen CI, Rossi A, Biran N, LeBlanc R, Grosicki S, Martelli M, Gunsilius E, Spicka I, Stevens DA, Facon T, Mesa MG, Zhang C, Van Domelen DR, Bentur OS, Gasparetto C. Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):e286-e296.e4. doi: 10.1016/j.clml.2023.06.001. Epub 2023 Jun 5.
- Bahlis NJ, Sutherland H, White D, Sebag M, Lentzsch S, Kotb R, Venner CP, Gasparetto C, Del Col A, Neri P, Reece D, Kauffman M, Shacham S, Unger TJ, Jeha J, Saint-Martin JR, Shah J, Chen C. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018 Dec 13;132(24):2546-2554. doi: 10.1182/blood-2018-06-858852. Epub 2018 Oct 23.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Belantamab mafodotin | Monoclonal antibody | 2.5 mg/kg | Intravenous |
| Subject | Bortezomib | Small molecule | 1.3 mg/m2 | Subcutaneous |
| Subject | Carfilzomib | Other / unclassified | 56 mg/m2 | Intravenous |
| Subject | Carfilzomib | Other / unclassified | 70 mg/m2 | Intravenous |
| Subject | Daratumumab | Monoclonal antibody | 16 mg/kg | Intravenous |
| Subject | Dexamethasone | Small molecule | 20 mg | Oral |
| Subject | Dexamethasone | Small molecule | 28 mg | Oral |
| Subject | Dexamethasone | Small molecule | 40 mg | Oral |
| Subject | Elotuzumab | Monoclonal antibody | 10 mg/kg | Intravenous |
| Subject | Elotuzumab | Monoclonal antibody | 20 mg/kg | Intravenous |
| Subject | Ixazomib | Unknown | 3 mg | Oral |
| Subject | Ixazomib | Unknown | 4 mg | Oral |
| Subject | Lenalidomide | Other / unclassified | 15 mg | Oral |
| Subject | Lenalidomide | Other / unclassified | 25 mg | Oral |
| Subject | Mezigdomide | Small molecule | 0.3 mg | Oral |
| Subject | Mezigdomide | Small molecule | 0.6 mg | Oral |
| Subject | Mezigdomide | Small molecule | 1 mg | Oral |
| Subject | Pomalidomide | Other / unclassified | 2 mg | Oral |
| Subject | Pomalidomide | Other / unclassified | 3 mg | Oral |
| Subject | Pomalidomide | Other / unclassified | 4 mg | Oral |
| Subject | Selinexor | Other / unclassified | 20 mg | Oral |
| Subject | Selinexor | Other / unclassified | 40 mg | Oral |
| Subject | Selinexor | Other / unclassified | 60 mg | Oral |
| Subject | Selinexor | Other / unclassified | 80 mg | Oral |
| Subject | Selinexor | Other / unclassified | 100 mg | Oral |
| Background | Clarithromycin | Small molecule | 500 mg | Oral |