- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT04891744
Selinexor in Combination With Thalidomide and Dexamethasone in RRMM
Phase Ib/II Study of ATG-010 in Combination With Thalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Li Zheng, M.D., Ph.D
- Telefonnummer: +86-028-85423655
- E-mail: lzheng2005618@163.com
Studiesteder
-
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Sichuan
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Chengdu, Sichuan, Kina, 610041
- West China Hospital of Sichuan University
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Kontakt:
- Li Zheng, MD.PhD
- Telefonnummer: +86-028-85423655
- E-mail: lzheng2005618@163.com
-
Ledende efterforsker:
- Ting Niu, M.D.,Ph.d
-
Ledende efterforsker:
- Li Zheng, M.D.,Ph.d
-
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: 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.
|
100 mg/d, Po. dag 1-28
Andre navne:
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.
Andre navne:
20 mg/d Po. on day 1, 2,8,9,15,16,22,23
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Samlet responsrate (ORR)
Tidsramme: Vurderet fra datoen for første dosis af undersøgelsesbehandlingen indtil den dato, hvor PD vurderede op til 12 måneder
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ORR i hver arm: delvis respons (PR) + meget god delvis respons (VGPR) + komplet respons (CR)
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Vurderet fra datoen for første dosis af undersøgelsesbehandlingen indtil den dato, hvor PD vurderede op til 12 måneder
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Progressionsfri overlevelse (PFS)
Tidsramme: 12 måneder
|
Varighed fra start af studiebehandling til PD eller død (uanset årsag), alt efter hvad der kommer først
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12 måneder
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Clinical Benefit Rate (CBR)
Tidsramme: 12 måneder
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Clinical Benefit Rate (CBR=ORR+Minor Response [MR])
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12 måneder
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Disease Control Rate (DCR)
Tidsramme: 12 måneder
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Disease Control Rate (DCR=CBR+Stable Disease[SD; i minimum 12 uger])
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12 måneder
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Antal deltagere med uønskede hændelser
Tidsramme: Fra første dosis af undersøgelseslægemidlet til afslutning af behandlingen (op til 12 måneder)
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Antal deltagere med behandlingsfremkomne bivirkninger (TEAE'er) og behandlingsfremkaldte alvorlige bivirkninger (TESAE'er)
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Fra første dosis af undersøgelseslægemidlet til afslutning af behandlingen (op til 12 måneder)
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Samlet overlevelse (OS)
Tidsramme: 12 måneder
|
Estimater af Kaplan-Meier
|
12 måneder
|
Minimal Residual Disease (MRD)
Tidsramme: 12 måneder
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At evaluere den minimale resterende sygdom hos CR- og sCR-patienter
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12 måneder
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Varighed af svar (DOR)
Tidsramme: 12 måneder
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Varighed fra den første observation af mindst PR til tidspunktet for sygdomsprogression eller dødsfald på grund af sygdomsprogression, alt efter hvad der indtræffer først.
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12 måneder
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Ting Niu, M.D., Ph.D, West China Hospital
- Ledende efterforsker: Li Zheng, M.D., Ph.D, West China Hospital
Datoer for undersøgelser
Studer store datoer
Studiestart (Forventet)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjerte-kar-sygdomme
- Karsygdomme
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Hæmatologiske sygdomme
- Hæmoragiske lidelser
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Myelomatose
- Neoplasmer, Plasmacelle
- Lægemidlers fysiologiske virkninger
- Anti-infektionsmidler
- Autonome agenter
- Agenter fra det perifere nervesystem
- Anti-inflammatoriske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antiemetika
- Gastrointestinale midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Angiogenese-hæmmere
- Angiogenesemodulerende midler
- Vækststoffer
- Væksthæmmere
- Antibakterielle midler
- Leprostatiske midler
- Dexamethason
- Thalidomid
Andre undersøgelses-id-numre
- ATG-010-IIT-MM-001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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