Multiple Myeloma
Conditions
Keywords
Selinexor, ATG-010, Multiple Myeloma, Relapsed/Refractory Multiple Myeloma, Thalidomide
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 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
Detailed description
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.
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.
DRUGThalidomide
100mg/d, Po. on day1-28
DRUGDexamethasone
20 mg/d Po. on day 1, 2,8,9,15,16,22,23
Sponsors
Li Zheng
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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. 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. 7. Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault). 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. 9. 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 10. Expected survival is more than 6 months. 11. 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) 12. 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. 13. 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 |
|---|---|---|
| Disease Control Rate (DCR) | 12 months | Disease Control Rate (DCR=CBR+Stable Disease\[SD; for a minimum of 12 weeks\]) |
| Progression-Free Survival (PFS) | 12 months | Duration from start of study treatment to PD or death (regardless of cause), whichever comes first |
| Overall Survival (OS) | 12 months | The estimates of Kaplan-Meier |
| 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. |
| Clinical Benefit Rate (CBR) | 12 months | Clinical Benefit Rate (CBR=ORR+Minor Response \[MR\]) |
| 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) |
| Minimal Residual Disease (MRD) | 12 months | To evaluate the minimal residual disease in CR and sCR patients |
Countries
China
Contacts
Primary ContactHongwei Li, MSc
Backup ContactLi Zheng, M.D., Ph.D
Outcome results
None listed