- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning 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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Förväntat)
Fas
- Fas 2
- Fas 1
Kontakter och platser
Studieorter
-
-
-
Düsseldorf, Tyskland, 40225
- University Hospital Düsseldorf
-
Essen, Tyskland, 45147
- University Hospital Essen
-
Frankfurt am Main, Tyskland, 60590
- University Hospital Frankfurt
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Hamburg, Tyskland, 20246
- University Hospital Hamburg-Eppendorf
-
Mainz, Tyskland, 55131
- University Hospital Mainz
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Marburg, Tyskland, 35043
- University Hospital Marburg
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Panobinostat Arm A
|
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Andra namn:
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
Andra namn:
|
Experimentell: Panobinostat Arm B
|
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Andra namn:
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
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
---|---|
Maximum tolerated dose (MTD) of panobinostat
Tidsram: after 28 days of administration
|
after 28 days of administration
|
Dose-limiting toxicity (MTD) of Panobinostat
Tidsram: after 28 days of administration
|
after 28 days of administration
|
Sekundära resultatmått
Resultatmått |
Tidsram |
---|---|
Cumulative incidence of hematologic relapse and death
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: one year after HSCT
|
one year after HSCT
|
Duration of complete donor chimerism
Tidsram: 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
Tidsram: one year after HSCT
|
one year after HSCT
|
patient-reported health-related quality of life
Tidsram: 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
|
Samarbetspartners och utredare
Utredare
- Huvudutredare: Gesine Bug, MD, Johann Wolfgang Goethe University Hospital
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Förväntat)
Avslutad studie (Förväntat)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Neoplasmer efter histologisk typ
- Neoplasmer
- Sjukdom
- Benmärgssjukdomar
- Hematologiska sjukdomar
- Precancerösa tillstånd
- Syndrom
- Myelodysplastiska syndrom
- Leukemi
- Leukemi, myeloid
- Leukemi, Myeloid, Akut
- Preleukemi
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antineoplastiska medel
- Histon deacetylashämmare
- Panobinostat
Andra studie-ID-nummer
- CLBH589 BDE05T
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