Multiple Myeloma
Conditions
Keywords
Selinexor（ATG-010）, Multiple Myeloma, Relapsed/Refractory Multiple Myeloma, Thalidomide, Pomalidomide, Lenalidomide
Brief summary
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 three arms, Selinexor(ATG-010) in Combination with Immunomodulator (Thalidomide/ Pomalidomide/ Lenalidomide）and Dexamethasone to Treat Relapsed/Refractory Multiple Myeloma Patients. To evaluate efficacy and safety of Selinexor in combination with Immunomodulator and Dexamethasone in RRMM patients received at least one prior lines of therapy.
Detailed description
This is a single-arm and open-label phase II study of Relapsed/Refractory Multiple Myeloma patients who have received at least one prior lines of treatment therapy; This study includes three experimental arms. Arm I is given XTd regimen (ATG-010 60mg/d QW, Thalidomide 100mg/d and Dexamethasone 40mg/d QW) in approximately 30 subjects. Arm II is given XRd regimen (ATG-010 60mg/d QW, Lenalidomide 25mg/d d1-21 and Dexamethasone 40mg/d QW) in approximately 30 subjects, Arm III is given XPd（ATG-010 60mg/d QW, Pomalidomide 4mg/d d1-21 and Dexamethasone 40mg/d QW ) in approximately 30 subjects,The three arms are 4 weeks per cycle and include a total of 12 cycles.
Interventions
DRUGSelinexor
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 60mg/d QW
DRUGThalidomide
100mg/d, Po. on day1-28
DRUGLenalidomide
PO,Lenalidomide 25mg once daily from D1-21
DRUGPomalidomide
Pomalidomide will be given at 4mg once daily for 21 days in a 28-day cycle, PO.
DRUGDexamethasone
Dexamethasone will be given at a dose of 40mg orally once a week for 4 weeks (D1,8,15,22).
Sponsors
Juan Du
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must meet all of the following inclusion criteria to be eligible to enroll in this study: 1. Known and written informed consent (ICF) voluntarily. 2. Age ≥ 18 years and ≤ 75 years. 3. 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. 4. At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria. 5. 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. 6. Left ventricular ejection fraction#LVEF #≥50% by an echocardiogram or MUGA scan in 42 days before the first administration 7. 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. 8. Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault). 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. 10. Measurable MM as defined by at least one of the following: 1. Serum M-protein (SPEP) ≥ 10 g/L 2. 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg) 3. Serum FLC ≥ 100 mg/L with abnormal FLC ratio 11. Expected survival is more than 6 months. 12. Adequate hematopoietic function (no blood transfusion within 2 weeks and no G-CSF/GM-CSF supportive treatment within 1 week prior to screening test): 1. Hemoglobin level ≥ 80 g/L 2. ANC ≥ 1,000/mm3 (1.0×109/L) 3. Platelet count ≥ 75,000/mm3 (75×109/L) 13. Female patients of childbearing potential must meet below two criteria: 1. 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. 2. 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. 14. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Assessed from the date of first dose of study treatment until the date that PD assessed up to 12months | ORR in each arm: partial response (PR) + very good partial response (VGPR) + complete response (CR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 12 months | The estimates of Kaplan-Meier |
| Progression-Free Survival (PFS) | 12 months | Duration from start of study treatment to PD or death (regardless of cause), whichever comes first |
| Duration of Response (DOR) | 12 months | Duration from the first observation of at least PR to time of disease progression, or deaths due to disease progression,whichever occurs first. |
| Minimal Residual Disease (MRD) | 12 months | To evaluate the minimal residual disease in CR and sCR patients |
| Disease Control Rate (DCR) | 12 months | Disease Control Rate (DCR=CBR+Stable Disease\[SD; for a minimum of 12 weeks\]) |
| Number of Participants with Adverse Events | From first dose of study drug administration to end of treatment (up to 12 months) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
| Clinical Benefit Rate (CBR) | 12 months | Clinical Benefit Rate (CBR=ORR+Minor Response \[MR\]) |
Countries
China
Contacts
Primary ContactJuan Du, M.D., Ph.D
Backup ContactHongwei Li, MSc
Outcome results
None listed