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) - BOSTO
- Conditions
- Relapsed or refractory multiple myeloma (RRMM)MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-003957-14-AT
- Lead Sponsor
- Karyopharm Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 364
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 FLC = 100 mg/L, provided that the serum FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65).
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 IMWG response criteria) on or after their most recent regimen.
4. Prior treatment with bortezomib or other 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 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 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. Patients with chronic, stable Grade 2 non-hematological toxicities may be included following approval from the Medical Monitor.
9. Adequate hepatic function within 28 days prior to C1D1:
a. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s
syndrome who must have a total bilirubin of < 3 × ULN), and b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 × ULN.
10. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance
[CrCl] of = 20 mL/min, calculated using the formula of Cockroft and Gault):
(140-Age) × Mass (kg)/(72 × creatinine mg/dL)
Multiply by 0.85 if the patient is female, or if CrCl is = 20 mL/min as measured by
24-hour urine collection.
11. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell
(WBC) count = 1500/mm3, absolute neutrophil count = 1000/mm3, hemoglobin =
8.5 g/dL and platelet count = 75,000/mm3 (patients for whom < 50% of bone marrow
nucleated cells are plasma cells) or = 50,000/mm3 (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 (eg,
eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between
growth factor support and the Screening assessments, but they may receive growth
factor support during the study.
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 stud
1. Prior exposure to a SINE compound, 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. Cancer treated with curative intent for > 5 years
previously and without evidence of recurrence will be allowed.
3. Has any concurrent medical condition or disease (eg, 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. Patients on prophylactic antibiotics or with a controlled
infection within 1 week prior to C1D1 are acceptable.
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 peripheral neuropathy or Grade = 2 peripheral 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 = 2 (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. BSA < 1.4 m2 at baseline, calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller, 1987) method.
17. Life expectancy of < 4 months.
18. Major surgery within 4 weeks prior to C1D1.
19. Active, unstable cardiovascular function:
a. Symptomatic ischemia, or
b. Uncontrolled clinically significant conduction abnormalities (eg, 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
c. Congestive heart failure of New York Heart Association Class = 3 or known left ventricular ejection fraction < 40%, or
d. 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 r
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method