- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT03336632
Chidamide Plus PTCy/Cyclosporine to Prevent GVHD After Myeloablative Conditioning, Matched PBSCT
Chidamide Plus Post-transplantation Cyclophosphamide and Cyclosporine to Prevent Graft-versus-host Disease After Myeloablative Conditioning, Matched Peripheral-blood Stem-cell Transplantation
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Eligible patients were aged 16 to 65 years, diagnosed with hematologic malignancy, and had a Karnofsky performance score of ≥70% and were candidates for myeloablative HCT. A 8/8 HLA allelic match between the donor and the recipient at HLA-A, HLA-B, HLA-C, and HLA-DRB1 by high-resolution typing was required. The graft source was PBSC.
Patients received a myeloablative conditioning regimen consisting of oral chidamide given twice weekly at a dose of 20 mg from day -7 to 2 weeks post transplantation, intravenous busulfan 3.2 mg/kg from day -6 to -3, intravenous fludarabine 30 mg/m2 and cytarabine 1g/m2 respectively from day -6 to -2. PBSCs were infused on day 0. GVHD prophylaxis was post-transplantation cyclophosphamide (50 mg/kg on day +3, +4) and cyclosporine (started from day +5). In the absence of GVHD, cyclosporine tapering started on day +100 and discontinued on day +180. Minimal residual disease (MRD) was determined by multi-parameter flow cytometry.
Studietype
Registrering (Forventet)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
Sichuan
-
Chengdu, Sichuan, Kina, 610044
- West China Hospital of Sichuan University
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Age ≥ 16 years or older, and ≤ 65 years at time of enrollment
- Signed informed consent
- Hematologic disorder requiring allogeneic hematopoietic cell transplantation
- Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
- Transaminases (AST, ALT) < 3 times upper limit of normal (ULN) values
- Creatinine clearance calculated ≥ 50 mL/min
- Karnofsky Performance Status Score ≥ 60%.
- Human leukocyte antigen (HLA) matched 8/ (A, B, C, DRB1) related or unrelated donor
Exclusion Criteria:
- Active infection not controlled with appropriate antimicrobial therapy HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
- Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) ≥4
- Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- Pregnancy
- Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first chidamide treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as heart rate (HR)< 45 bpm (Patients with pacemakers are eligible if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF > 480 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., New York Heart Association (NYHA) class III or IV , uncontrolled hypertension) as per discretion of principal investigator and/or treating physician; Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs listed on Appendix B of study documents that are required for hematopoietic cell transplantation (HCT) patients.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Chidamide
Chidamide, tablets, 5 mg/tablet, 20 mg orally twice weekly from D-7~+14 Cyclophosphamide: 50 mg/Kg intravenously D+3, +4 Cyclosporine A: intravenously then orally 3 mg/Kg D+5~D+100
|
20 mg orally, twice weekly from D-7 to D+14
Andre navn:
50 mg/Kg intravenously D+3, +4
3 mg/Kg intravenously then orally from D+5 to D+100 if no acute graft-versus-host disease
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
aGVHD
Tidsramme: 100 day after infusion of PBSCs
|
accumulated incidence of aGVHD
|
100 day after infusion of PBSCs
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
GRFS
Tidsramme: 3 years after recruitment
|
GVHD free, relapse free survival
|
3 years after recruitment
|
|
DFS
Tidsramme: 3 years after recruitment
|
Disease free survival
|
3 years after recruitment
|
|
OS
Tidsramme: 3 years after recruitment
|
Overall survival
|
3 years after recruitment
|
|
cGVHD
Tidsramme: 2 yeas after infusion of PBSCs
|
accumulated incidence of cGVHD
|
2 yeas after infusion of PBSCs
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studiestol: Ting Liu, MD, West China Hospital
Studierekorddatoer
Studer hoveddatoer
Studiestart (Forventet)
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Enzymhemmere
- Antirevmatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Dermatologiske midler
- Antifungale midler
- Calcineurin-hemmere
- Cyklofosfamid
- Syklosporin
- Syklosporiner
Andre studie-ID-numre
- HX-GVHD-1
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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