A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM.

Официальное название

A Phase 2b, Open-label, Multi-arm Clinical Trial of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma or Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory Multiple Myeloma

Обзор

The purpose of this study is to assess the efficacy, antitumor activity, safety and tolerability of selinexor plus low-dose dexamethasone in participants with penta-refractory multiple myeloma or selinexor and bortezomib plus low-dose dexamethasone in participants with triple-class refractory multiple myeloma.

Вмешательства

• Препарат Selinexor
  Participants will receive Selinexor oral tablets.
• Препарат Dexamethasone
  Participants will receive Dexamethasone oral tablets.
• Препарат Bortezomib
  Participants will receive Bortezomib SC injection.

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: From the date of randomization up to death (approximately 60 months)]

Вторичные конечные точки (7)

• Duration of Response (DOR) [Срок оценки: From the date of randomization to first disease progression or death (approximately 60 months)]
• Clinical Benefit Rate (CBR) [Срок оценки: From the date of randomization up to death (approximately 60 months)]
• Disease control rate (DCR) [Срок оценки: From the date of randomization up to death (approximately 60 months)]
• Progression-Free Survival (PFS) [Срок оценки: From the date of randomization to first disease progression or death (approximately 60 months)]
• Overall Survival (OS) [Срок оценки: From the date of randomization up to death (approximately 60 months)]
• Time to Next Treatment (TTNT) [Срок оценки: From the date of first dose up to death (approximately 60 months)]
• Number of Participants with Adverse Events (AE) [Срок оценки: From start of study drug administration up to follow-up (approximately 60 months)]

Критерии участия

Критерии включения

• Age greater than or equal to (>=)18 years at the time of signing informed consent.
• Written informed consent in accordance with federal, local, and institutional guidelines.
• Measurable MM based on IMWG guidelines as defined by at least one of the following:

• Serum M-protein >= 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA.
• Urinary M-protein excretion >= 200 mg/24 hours.
• Free light chain (FLC) >= 100 milligram per liter (mg/L), provided that the FLC ratio is abnormal.
• Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW prior to protocol version (PV) 5.0: Participants must have relapsed or refractory multiple myeloma (RRMM) and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 proteasome inhibitors (PIs), at least 2 immunomodulatory agent (IMiDs), and 1 anti-cluster of differentiation (CD38) monoclonal antibody. Refractory is defined as lesser than or equal to (<=) 25 percent (%) response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
• Only for Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Participants must have RR MM and have been previously treated with >=3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as <=25% response to therapy or progression during therapy or progression within 60 days after completion of therapy.
• Only for arm SVd: Participants must have previously received 1 to 5 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti- CD38 monoclonal antibody.
• Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
• Female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment.

Критерии исключения

• Active plasma cell leukemia.
• Documented systemic amyloid light chain amyloidosis.
• Active central nervous system MM.
• Only for SVd arm: Greater than Grade 2 peripheral neuropathy or Grade >= 2 peripheral neuropathy with pain at baseline, regardless of whether or not the participant is currently receiving medication.
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) <= 2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1).
• Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1.
• Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade greater than (>) 2 at C1D1.
• Inadequate hepatic function defined as total bilirubin >= 2x upper limit of normal (ULN) (>= 3x ULN for participants with Gilbert's syndrome), aspartate transaminase (AST) >= 2.5x ULN, and alanine transaminase (ALT) >= 2.5x ULN.
• Inadequate renal function defined as estimated creatinine clearance of lesser than (<) 20 milliliter per minute (mL/min), calculated using the formula of Cockroft and Gault.
• Inadequate hematopoietic function defined as the following:

• Absolute neutrophil count (ANC) < 1000/cubic millimeter (mm\^3)
• Platelet count < 75,000/mm\^3
• Hemoglobin (Hb) level < 8.5 g/dL
• Life expectancy of < 4 months, based on the opinion of the Investigator.
• Major surgery within 4 weeks prior to C1D1.
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.
• Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.
• Female participants who are pregnant or lactating.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1.
• Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
• Prior exposure to a SINE compound, including selinexor.
• Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with the participation in the study.
• Contraindication to any of the required concomitant drugs or supportive treatments.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Израиль · 12 центров

• Emek Medical Center — Afula
• Assuta Ashdod Medical Center — Ashdod
• Bnai-Zion Medical Center — Haifa
• Rambam Health Care Campus — Haifa
• Shaare Zedek Medical Center — Jerusalem
• Hadassah Medical Center — Jerusalem
• Rabin Medical Center (Beilinson Hospital) — Petah Tikva
• The Chaim Sheba Medical Center at Tel HaShomer — Ramat Gan
• … и ещё 4 центра

Греция · 4 центра

• University General Hospital of Patras — Pátrai
• General Hospital of Athens "Alexandra" — Attiki
• General Hospital of Athens "Evangelismos" — Athens
• Theageneion Cancer Hospital — Thessaloniki

Публикации

• 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. PMID 38826786

Идентификаторы

NCT: NCT04414475 · XPORT-MM-028

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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