This is a single-arm and open-label study to explore XVRd (ATG-010, Bortezomib, Lenalidomide and Dexamethasone) regimen in high-risk newly diagnosed multiple myeloma.The primary objective of the dose escalation study is to determine the safety, tolerability, and recommended phase II dose (RP2D) of selinexor; Then dose expansion at the RP2D level based on dose escalation phase will be conducted to evaluate the efficacy, safety and tolerability.The enrollment period for this study is expected to be approximately 12 months. The study will end when all patients have completed 12 cycles treatment/follow-up since the initiation of the study drug, or the last patient has expired, has been lost to follow-up, or has withdrawn consent, whichever occurs first.
This is a single-arm and open-label study to explore XVRd (ATG-010, Bortezomib, Lenalidomide and Dexamethasone) regimen in high-risk newly diagnosed multiple myeloma. Approximately 3-42 patients will be enrolled in the study. In dose escalation phase, patients with high-risk NDMM will be treated with VRd standard regimen (bortezomib 1.3mg/m2 SC on day1,4,8,11, lenalidomide 25 mg on day 1-14 and dexamethasone 40mg on day 1,8,15 in a 21-day cycle) plus escalating doses of selinexor 40 mg or 60 mg on days 1, 8, and 15 of each cycle in a 3+3 design. The primary objective of the dose escalation study is to determine the safety, tolerability,and recommended phase II dose (RP2D) of selinexor; Then dose expansion at the RP2D level based on dose escalation phase will be conducted to evaluate the efficacy, safety and tolerability. All of the patients will receive 12 cycles of XVRd , and subjects can choose maintenance treatment with XR after 12 cycles of XVRd.The primary objective of the dose escalation study is to determine the safety, tolerability, and recommended phase II dose (RP2D) of selinexor; Then dose expansion at the RP2D level based on dose escalation phase will be conducted to evaluate the efficacy, safety and tolerability. The enrollment period for this study is expected to be approximately 12 months. The study will end when all patients have completed 12 cycles treatment/follow-up since the initiation of the study drug, or the last patient has expired, has been lost to follow-up, or has withdrawn consent, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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. Selinexor dose escalation: 40, 60mg respectively on day 1,8,15 for 21 days cycles
The investigators gave patients subcutaneous bortezomib 1.3mg/sqm on days 1, 8,15 of a 21- day cycle. standard bortezomib-lenalidomide-dexamethasone
The investigators gave patients oral lenalidomide 25mg on days 1 to 14 of a 21-day cycle. standard bortezomib-lenalidomide-dexamethasone
The investigators gave patients oral dexamethasone 40mg on days 1, 8, 15 of a 21-day cycle. standard bortezomib-lenalidomide-dexamethasone
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China,
Guangzhou, Guangdong, China
RECRUITINGSun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGNanfang Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGDose Escalation: Maximum Tolerated Dose (MTD)
The MTD will be determined by study definition as the highest dose level without significant safety and tolerability concern.
Time frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days) ;
Dose Escalation: Recommended Phase 2 Does (RP2D)
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
Time frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days) ;
Dose Expansion: MRD negative remission
MRD negative remission (\<10-5) as defined by IMWG consensus
Time frame: At any time up to 12 months after XVRD treatment
complete response (CR)
complete response (CR) and stringent complete response (sCR)
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a VGPR, CR or PR (up to 12 cycles)
Overall Survival (OS)
Occurrence of death regardless of cause
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
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
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR=ORR+Minor Response \[MR\])
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
Number of Participants with Adverse Events
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug administration to end of treatment (up to 12 months)
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