A Phase II study of Selinexor (KPT-330) combined with bortezomib and dexamethasone (SVd) for induction and consolidation for patients with progressive or refractory Multiple Myeloma.
- Conditions
- Multiple Myeloma10018865
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 49
•The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
•Age >= 18 years at the time of signing the informed consent form.
•Able to adhere to the study visit schedule and other protocol requirements.
•Documented diagnosis of multiple myeloma and measurable disease (serum M-protein >= 5 g/L or urine M-protein >= 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/L);
•Documented progression as per the IMWG uniform response criteria (Durie, 2006) during or after the anti-myeloma regimen; or never achieved a response better than PD after at least 2 cycles of their previous anti-myeloma regimen.
•At lease one prior anti-myeloma regimen. Induction therapy followed by autologous stem cell transplant (ASCT) and consolidation/ maintenance will be considered as one regimen.
•Normal renal function with a Creatinine Clearance > 30mL/min according to the Modification of Diet in Renal Disease (MDRD) equation for estimation of Glomerular Filtration Rate (GFR)
•WHO performance status score of 0, 1 or 2
•Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
•All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
•All subjects must agree not to share medication.
•Prior resistance/refractory disease to bortezomib, defined as progression during or within 60 days of completing bortezomib therapy.
•Systemic AL amyloidosis
•Non secretory myeloma
•Known CNS involvement
•Absolute neutrophil count (ANC) <1.0 x 109/L, unless related to MM.
•Platelet count < 50 x 109/L.
•Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).
•Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted).
•Significant hepatic dysfunction (Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) or serum total bilirubin > 2 x ULN unless due to inheritable syndrome such as Gilbert*s)
•Prior history of malignancies, other than MM, unless the subject has been free of the disease
for >= 5 years. Exceptions include the following:
oBasal or squamous cell carcinoma of the skin.
oCarcinoma in situ of the cervix or breast.
oIncidental histological finding of prostate cancer (TNM stage of T1a or T1b).
•Hypersensitivity to bortezomib or dexamethasone (this includes >= Grade 3 rash during prior bortezomib therapy).
•Peripheral neuropathy >= Grade 2 at time of registration.
•Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment
•Congestive heart failure (NY Heart Association Class III or IV).
•Myocardial infarction within 12 months prior to starting study treatment
•Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
•Subjects who received any of the following within the last 14 days of initiation of study treatment:
•Major surgery (kyphoplasty is not considered major surgery).
•Use of any anti-myeloma drug therapy at the time of registration in the trial.
•Use of any investigational agents within 28 days or five half-lives (whichever is longer) of treatment.
•Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form.
•Any active uncontrolled infections
•Pregnant or breastfeeding females.
•Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B or C or chronic hepatitis B or C.
•Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase I<br /><br><br /><br>•Dose-limiting toxicity (DLT) as defined in paragraph 4.1, and recommended<br /><br>phase II dose (RDL) of selinexor when combined with bortezomib and dexamethasone<br /><br><br /><br>Phase II<br /><br><br /><br>•(s)CR+VGPR rate. In order for patients to be considered as a success for the<br /><br>primary endpoint, a VGPR or (s)CR must be documented during or following<br /><br>induction or consolidation treatment, according to criteria in appendix E. All<br /><br>other patients will be considered as not having achieved at least a VGPR. In<br /><br>this analysis we will considered the best response obtained during<br /><br>induction/consolidation chemotherapy.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase I<br /><br><br /><br>•Toxicity<br /><br><br /><br>Phase II<br /><br><br /><br>•Response (sCR, CR, VGPR, PR) after induction and after consolidation<br /><br>•Toxicity<br /><br>•Progression free survival (PFS; i.e. time from registration to progression or<br /><br>death from any cause, whichever comes first)<br /><br>•Overall survival (OS) measured from registration. Patients still alive or lost<br /><br>to follow up are censored at the date they were last known to be alive</p><br>