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A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM) - BOSTON

Studio Clinico

Patologia: Mieloma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: No

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

1. Histologically confirmed MM with measurable disease per IMWG guidelines 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 myeloma, by quantitative serum IgA levels; or
b. Urinary M-protein excretion at least 200 mg/24 hours; or
c. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.
2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.
3. Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen.
4. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met:
- Best response achieved with prior bortezomib at any time was ≥ PR and with the last PI (PI therapy (alone or in combination) was ≥ PR, AND
- Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND
- Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.
5. Must have an ECOG Status score of 0, 1, or 2.
6. Written informed consent in accordance with federal, local, and institutional guidelines.
7. Age ≥18 years.
8. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.
9. Adequate hepatic function within 28 days prior to C1D1.
10. Adequate renal function within 28 days prior to C1D1.
11. Adequate hematopoietic function within 7 days prior to C1D1.
12. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.

Criteri di esclusione: 

1. Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.
2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization.
3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
5. Active plasma cell leukemia.
6. Documented systemic light chain amyloidosis.
7. MM involving the central nervous system.
8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
9. Spinal cord compression.
10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication
11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies) ≤ 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. 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.
13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1.
14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
15. Pregnant or breastfeeding females.
16. Body Surface Area < 1.4 m² at baseline, calculated by the Dubois or Mosteller method.
17. Life expectancy of < 4 months.
18. Major surgery within 4 weeks prior to C1D1.
19. Active, unstable cardiovascular function:
    1.Symptomatic ischemia, or
    2.Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
    3.Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or
    4.Myocardial infarction within 3 months prior to C1D1.
20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity
21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
22. 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.
23. 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.
24. Contraindication to any of the required concomitant drugs or supportive treatments.
25. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.

Trattamento sperimentale: 

Selinexor+Bortezomib+Dexamethasone (SVd)

Trattamento di controllo: 

Bortezomib+Dexamethasone (Vd)

Obiettivi primari dello studio: 

Compare progression-free survival (PFS) based on the Independent Review Committee's (IRC's) disease outcome assessments in patients randomized to the SVd Arm versus the Vd Arm [ Time Frame: 15 months ]

PFS, defined as time from date of randomization until the first date of PD, per International Myeloma Working Group (IMWG) response criteria, or death due to any cause, whichever occurs first. For the purposes of PFS determination, PD will be determined by the IRC

Centri partecipanti

Nord Italia

Ospedale Papa Giovanni XXIII Bergamo
Piazza OMS 1 - 24127 Bergamo - BG

Riferimento: Prof. Alessandro Rambaldi
Telefono: 0352673683
Email: arambaldi@asst-pg23.it

 

Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO

Riferimento: Prof. Michele Cavo
Email: michele.cavo@unibo.it

 

IRCCS A.O.U. San Martino - IST
Largo Rosanna Benzi 10 - 16132 Genova - GE

Riferimento: Prof. Marco Gobbi
Email: gobbi@unige.it

 

Ospedale Niguarda Ca' Granda
Piazza dell'Ospedale Maggiore 3 - 20162 Milano - MI

Riferimento: Dr.ssa Anna Maria Cafro
Email: annamaria.cafro@ospedaleniguarda.it

 

AOU Città della Salute e della Scienza di Torino
Corso Bramante 88 - 10126 Torino - TO

Riferimento: Dr.ssa Sara Bringhen
Telefono: 0116334260
Email: sbringhen@cittadellasalute.to.it

 

Centro Italia

Ospedale Riuniti Umberto I - Lancisi-Salesi
Via Conca 71 - 60020 Ancona - AN

Riferimento: Dr. Massimo Offidani
Email: Massimo.Offidani@ospedaliriuniti.marche.it

 

AOU Careggi
Largo Brambilla 3 - 50134 Firenze - FI

Riferimento: Prof. Alberto Bosi
Email: alberto.bosi@unifi.it

 

Università La Sapienza Policlinico Umberto I
Viale del Policlinico 155 - 00161 Roma - RM

Riferimento: Prof. Roberto Foà
Telefono: 0685795753
Email: rfoa@bce.uniroma1.it

 

AO S. Maria Terni
Via Tristano di Joannuccio 1 - 05100 Terni - TR

Riferimento: Prof.ssa Anna Marina Liberati
Email: marina.liberati@unipg.it

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT03110562

Data di inserimento: 21.01.2019

Promotore

Karyopharm Therapeutics Inc

CRO

/

Principal Investigator ITALIA

ASST Papa Giovanni XXIII, Dipartimento di Oncologia e Ematologia - Bergamo

Riferimento: Dr. Alessandro Rambaldi

Telefono: 0352673683

Email: arambaldi@asst-pg23.it

Localita: Bergamo

 

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