Selinexor in Combination With Thalidomide and Dexamethasone in RRMM
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Selinexor, ATG-010, Multiple Myeloma, Relapsed/Refractory Multiple Myeloma, Thalidomide
Eligibility Criteria
Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
- Known and written informed consent (ICF) voluntarily.
- Age ≥ 18 years and ≤ 75 years.
- Patients with multiple myeloma who have received first-line treatment (induction, autologous transplantation and maintenance as the same first-line treatment) and achieved at least partial remission in induction.
- At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria.
- Any clinically significant non-hematological toxicities (except for hair loss, peripheral neuropathy, which is otherwise stipulated in Article 13 of the exclusion criteria) that relevant to previous therapies must have resolved to ≤Grade 2 prior to first dose of study drug.
- Adequate hepatic function: total bilirubin < 2× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of < 3× ULN is required), AST < 2.5× ULN, and ALT < 2.5× ULN.
- Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
Measurable MM as defined by at least one of the following:
- Serum M-protein (SPEP) ≥ 10 g/L
- 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
- Serum FLC ≥ 100 mg/L with abnormal FLC ratio
- Expected survival is more than 6 months.
Adequate hematopoietic function (no blood transfusion within 2 weeks and no G-CSF/GM-CSF supportive treatment within 1 week prior to screening test):
- Hemoglobin level ≥ 80 g/L
- ANC ≥ 1,000/mm3 (1.0×109/L)
- Platelet count ≥ 75,000/mm3 (75×109/L)
Female patients of childbearing potential must meet below two criteria:
- must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment.
- must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential.
- Male patients (including those who have received vasectomy) must use a condom if sexually active with a female of child-bearing potential throughout the study and for 3 months following the last dose of study treatment.
Exclusion Criteria:
Patients who meet any of the following criteria will not be enrolled:
- Asymptomatic (smoldering) MM.
- Plasma cell leukemia.
- Documented active amyloidosis.
- Previously refractory or intolerant to immunomodulators.
- Pregnancy or breastfeeding.
- Major surgery was performed within 4 weeks prior to the first study.
Patients with active, unstable cardiovascular diseases, fits any of the following:
- Symptomatic ischemia, or
- Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with first-degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) are allowed), or
- Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3, or
- Acute myocardial infarction (AMI) within 3 months prior to the first dose of study drug.
- Uncontrolled active infection within 1 week prior to the first dose of study drug.
- Known HIV positive.
Known active hepatitis A, B, or C infection; or known positive for HCV RNA or HBsAg.
(Note: patients with HBsAg negative but HBc Ab positive need further HBV-DNA test, excluded if HBV-DNA ≥103 , if HBV-DNA <103 need anti-viral drugs)
- Prior malignancy that required treatment or has shown evidence of recurrence (except for skin basal-cell carcinoma and in-situ carcinoma including squamous cell carcinoma, bladder cancer in situ, endometrial cancer in situ, cervical cancer in situ/atypical hyperplasia, prostate cancer incidental finding (T1a or T1b), or breast cancer in situ) within 5 years prior to the first dose of study drug.
- Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
- Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 3 weeks prior to the first dose of study drug.
- Previous history of deep vein thrombosis.
- Serious, active psychiatric, or medical conditions which, in the opinion of the Investigator, could interfere with study treatment.
- Participation in an investigational anti-cancer clinical study within 3 weeks or 5 half-lives (T1/2) prior to the first dose of study drug.
- Received ASCT within 12 weeks prior to the first dose of study drug or previous allogeneic stem cell transplantation (no time limitation).
- Treatment with an approved or trial anticancer drug was given within 4 weeks prior to the first study.
- Known intolerance to or contraindication for glucocorticoid therapy.
- Prior exposure to a SINE compound.
Sites / Locations
- West China Hospital of Sichuan University
Arms of the Study
Arm 1
Experimental
Selinexor in combination with thalidomide and Dexamethasone
Selinexor in combination with thalidomide and Dexamethasone. Thalidomide will be given at 100mg/d d1-28,and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. Treatment will be administered in 28-day cycles,include a total of 12 cycles. Selinexor dose escalation: 60, 80, 100mg respectively on day 1,8,15,22 for 4-week cycles. Then Selinexor will be given at the recommended dose level on phase II.