Multiple myeloma (MM) is an incurable plasma cell cancer that almost all patients eventually relapse despite advancement in treatment strategies. B-cell maturation antigen (BCMA) is a cell surface receptor that expressed primarily by malignant and normal plasma cells. This is a single-arm that includes escalation phase and expansion phase ,Selinexor in Combination withThalidomide and Dexamethasone to Treat Relapsed/Refractory Multiple Myeloma Patients.To evaluate efficacy and safety of Selinexor in combination with Thalidomide and Dexamethasone in RRMM patients received at least one prior lines of therapy
This is a single-arm and open-label phase Ib/IIa study of Relapsed/Refractory Multiple Myeloma patients who have received at least one prior lines of treatment therapy; Approximately 3-48 patients will be enrolled in the study. In dose escalation phase, patients with RRMM will be treated with thalidomide 100mg/d, dexamethasone 20mg biweekly, and escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability. This arm is 4 weeks per cycle and include a total of 12 cycles.Selinexor RP2D,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. If a patient develops partial intolerance to glucocorticoids (as determined by the Investigator) during the study, a dose reduction of dexamethasone maximum to 10 mg is permitted. If patients do not tolerate this dose, a potential discontinuation or further dose reduction would be allowed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Selinexor (ATG-010# is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus along with inhibition of translation of oncoprotein mRNAs.
100mg/d, Po. on day1-28
20 mg/d Po. on day 1, 2,8,9,15,16,22,23
West China Hospital of Sichuan University
Chengdu, Sichuan, China
Overall Response Rate (ORR)
ORR in each arm: partial response (PR) + very good partial response (VGPR) + complete response (CR)
Time frame: Assessed from the date of first dose of study treatment until the date that PD assessed up to 12months
Duration of Response (DOR)
Duration from the first observation of at least PR to time of disease progression, or deaths due to disease progression, whichever occurs first.
Time frame: 12 months
Disease Control Rate (DCR)
Disease Control Rate (DCR=CBR+Stable Disease\[SD; for a minimum of 12 weeks\])
Time frame: 12 months
Progression-Free Survival (PFS)
Duration from start of study treatment to PD or death (regardless of cause), whichever comes first
Time frame: 12 months
Overall Survival (OS)
The estimates of Kaplan-Meier
Time frame: 12 months
Minimal Residual Disease (MRD)
To evaluate the minimal residual disease in CR and sCR patients
Time frame: 12 months
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR=ORR+Minor Response \[MR\])
Time frame: 12 months
Number of Participants with Adverse Events
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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Time frame: From first dose of study drug administration to end of treatment (up to 12 months)