- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01451268
Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) (PANOBEST)
Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk MDS or AML (PANOBEST)
The study's primary objective is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after hematopoietic stem cell transplantation (HSCT) and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).
Secondary objectives are
- To determine safety and tolerability of panobinostat
- To determine overall and disease-free survival at 12 months after HSCT
- To evaluate immunoregulatory properties of panobinostat
- To evaluate patient-reported health-related quality of life (HRQL)
The hypothesis of this study is that panobinostat can be an effective drug in preventing relapse of MDS and AML patients with high-risk features after hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC-HSCT) while at the same time reducing graft-versus-host disease (GvHD) with preservation of graft-versus-leukemia (GvL) effect.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Forventet)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
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Düsseldorf, Tyskland, 40225
- University Hospital Düsseldorf
-
Essen, Tyskland, 45147
- University Hospital Essen
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Frankfurt am Main, Tyskland, 60590
- University Hospital Frankfurt
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Hamburg, Tyskland, 20246
- University Hospital Hamburg-Eppendorf
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Mainz, Tyskland, 55131
- University Hospital Mainz
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Marburg, Tyskland, 35043
- University Hospital Marburg
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
AML (except acute promyelocytic leukemia, AML M3) with high-risk features defined as one or more of the following criteria:
- refractory to or relapsed after at least one cycle of standard chemotherapy
- > 10% bone marrow blasts at day 15 of the first induction cycle
- adverse risk cytogenetics including complex karyotype (≥ 3 abnormalities or abnormalities of chromosomes 3, 5 or 7) regardless of stage
- secondary to MDS or radio-/chemotherapy or
- MDS RAEB according to the WHO classification or intermediate-2 or high-risk according to IPSS or
Chronic myelomonocytic leukemia (CMML) with ≥ 5% bone marrow blasts and
- Allogeneic HSCT with reduced intensity conditioning (see Section 15.1 for definition) performed within 60 - 150 days prior to study entry
- Complete hematologic remission documented by bone marrow aspiration within 28 days prior to study entry
Exclusion Criteria:
- Active acute GvHD overall grade 2 - 4
- Prior treatment with a deacetylase (DAC) inhibitor
- Patients with impaired cardiac function or other concurrent severe and/or uncontrolled medical conditions
- Clinical symptoms suggesting central nervous system (CNS) leukemia
- Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Panobinostat Arm A
|
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Andre navn:
Start of Arm B after completion of Arm A; initial dose-level: one level below MTD of Arm A; 10mg upto 60mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every other week; duration: one year
Andre navn:
|
Eksperimentell: Panobinostat Arm B
|
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Andre navn:
Start of Arm B after completion of Arm A; initial dose-level: one level below MTD of Arm A; 10mg upto 60mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every other week; duration: one year
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
Maximum tolerated dose (MTD) of panobinostat
Tidsramme: after 28 days of administration
|
after 28 days of administration
|
Dose-limiting toxicity (MTD) of Panobinostat
Tidsramme: after 28 days of administration
|
after 28 days of administration
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
Cumulative incidence of hematologic relapse and death
Tidsramme: one year after HSCT
|
one year after HSCT
|
Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy
Tidsramme: patients will be followed for up to 2 years depending on the duration of study participation
|
patients will be followed for up to 2 years depending on the duration of study participation
|
Time to complete donor chimerism
Tidsramme: patients will be followed for up to 2 years depending on the duration of study participation
|
patients will be followed for up to 2 years depending on the duration of study participation
|
Cumulative incidence of extensive chronic GvHD
Tidsramme: one year after HSCT
|
one year after HSCT
|
Duration of complete donor chimerism
Tidsramme: patients will be followed for up to 2 years depending on the duration of study participation
|
patients will be followed for up to 2 years depending on the duration of study participation
|
Cumulative incidence of severe acute GvHD
Tidsramme: one year after HSCT
|
one year after HSCT
|
patient-reported health-related quality of life
Tidsramme: after 3 months of administration and one month after last intake of study drug
|
after 3 months of administration and one month after last intake of study drug
|
Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Gesine Bug, MD, Johann Wolfgang Goethe University Hospital
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
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
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Neoplasmer etter histologisk type
- Neoplasmer
- Sykdom
- Benmargssykdommer
- Hematologiske sykdommer
- Forstadier til kreft
- Syndrom
- Myelodysplastiske syndromer
- Leukemi
- Leukemi, myeloid
- Leukemi, Myeloid, Akutt
- Preleukemi
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antineoplastiske midler
- Histon deacetylase-hemmere
- Panobinostat
Andre studie-ID-numre
- CLBH589 BDE05T
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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