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Selinexor and Backbone Treatments of Multiple Myeloma Patients

RecruitingPhase 1, Phase 2Ages 18 Years - anyAllKaryopharm Therapeutics Inc
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In plain words

What the trial is, and whether it could suit you

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

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
Inclusion Criteria: 1. Written informed consent signed in accordance with federal, local, and institutional guidelines. 2. Age greater than or equal to (≥) 18 years at the time of informed consent. 3. Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma. 4. Symptomatic MM, based on IMWG guidelines. 5. Patients must have measurable disease as defined by at least one of the following: 1. Serum M-protein ≥ 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for immunoglobulin A (IgA) myeloma, by quantitative IgA 2. Urinary M-protein excretion at least 200 mg/24 hours 3. Serum free light chain (FLC) ≥ 100 milligram per liter (mg/L), provided that FLC ratio is abnormal 4. If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA MM), then quantitative immunoglobulin (Ig) levels by nephelometry or turbidometry are acceptable 6. Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to less than or equal (≤) Grade 2 by C1D1. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. 8. Adequate hepatic function within 28 days prior to C1D1: * For SPd, SRd, and SPEd: Total bilirubin \< 2\* upper limit of normal (ULN) (except patients with Gilbert's syndrome \[hereditary indirect hyperbilirubinemia\] who must have a total bilirubin of ≤ 3\* ULN) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5\* ULN * For SVd, SPVd, SDd, SNd, SBd and SDPd: Total bilirubin of \< 1.5\* ULN (except patients with Gilbert's syndrome \[hereditary indirect hyperbilirubinemia\] who must have a total bilirubin of ≤ 3\* ULN) and both AST and ALT \< 2.0\* ULN * For SKd and SMd: Total bilirubin \< 2x ULN (except patients with Gilbert's syndrome \[hereditary indirect hyperbilirubinemia\] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT \< 3.0x ULN 9. Adequate renal function within 28 days prior to C1D1. For Arms 1-11, estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976). * ≥ 20 milliliter per minute (mL/min) for SVd, SDd, and SKd arms * ≥ 30 mL/min for SNd, SBd, and SMd arms * ≥ 45 mL/min for SPd, SPVd, SPEd and SDPd arms * \> 60 mL/min for SRd arm 10. Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 100,000/mm\^3. * SPVd (Arm 4) and SKd (Arm 6) only: platelet count ≥150,000. * SMd (Arm 12) only: platelet count ≥75,000 for subjects in whom \<50% of bone marrow nucleated cells are plasma cells; or platelet count \<50,000 for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells. 11. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients must use highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment. For Arm 12 (SMd), all study subjects must agree and adhere to all testing and contraception requirements as specified in the mezigdomide Global Pregnancy Prevention Plan (PPP) SPd (Arm 1) Only. 12. Relapsed or refractory MM with: 1. Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM) 2. ≤ 25 percent (%) response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM) 3. Previously undergone ≥ 2 cycles of lenalidomide and a PI (in separate therapeutic regimens \[not for maintenance\] or in combination) 4. In the expansion arm at RP2D, patients must not be pomalidomide refractory SVd (Arm 2) Only: 13. Relapsed or refractory MM with: 1. Documented evidence of relapse after ≥ 1 previous line of therapy 2. Not refractory to bortezomib in their most recent line of therapy SRd in RRMM (Arm 3) Only: 14. Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient's MM was not refractory to prior lenalidomide; patients whose MM was refractory to lenalidomide maintenance regimens will be allowed in this cohort). SPVd (Arm 4) Only: 15. Patients who received 1- 3 prior lines of therapy, including ≥ 2 cycles of lenalidomide and have demonstrated disease progression on their last therapy (may include prior bortezomib, as long as the patient's MM was not refractory to bortezomib therapy), but patients must be pomalidomide-naïve in the Dose Expansion at RP2D (Cohort 4.3 ONLY). SDd (Arm 5) Only: 16. Patients who received ≥ 3 prior lines of therapy, including a PI and an immunomodulatory agent (IMiD), or patients with MM refractory to both a PI and an IMiD. 17. Patients must not have received prior anti-cluster of differentiation 38 (anti-CD38) monoclonal antibodies (Cohort 5.3 ONLY - Dose Expansion at RP2D). SKd (Arm 6) Only: 18. Patients may have received prior PIs; however, their MM must NOT be refractory to carfilzomib. SRd in NDMM (Arm 7) Only: 19. Patients must have symptomatic myeloma per IMWG guidelines with either CRAB criteria (calcium elevation, renal failure, anemia, lytic bone lesions) or myeloma-defining events and need systemic therapy. No prior systemic therapy for NDMM is permitted other than pulse dose dexamethasone (maximum dose of 160 mg) or corticosteroid equivalent. SNd (Arm 8) Only: 20. Patients must have MM that relapsed after 1 - 3 prior lines of therapy (may not include those with MM refractory to bortezomib or carfilzomib but patients must be ixazomib-naïve). SPEd (Arm 9) Only: 21. Patients who received ≥ 2 prior therapies, including lenalidomide and a proteasome inhib
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What it tests

  • Selinexor
  • Dexamethasone
  • Lenalidomide
  • Pomalidomide
  • Bortezomib
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Where

25 sites
Banner MD Anderson Cancer Center
Gilbert, United States
Jonnsson Comprehensive Cancer Center / University of Los Angeles
Los Angeles, United States
Sarah Cannon-Colorado Blood Cancer Institute
Denver, United States
Massachusetts General Hospital
Boston, United States
Dana Farber Cancer Institute
Boston, United States
University of Nebraska Medical Center
Omaha, United States
Hackensack University Medical Center - John Theurer Cancer Center
Hackensack, United States
Columbia University
New York, United States

…and 17 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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