Clinical trial 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)
Official title: Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk MDS or AML (PANOBEST)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Keywords: 60 to 150 Days After Allogeneic Stem Cell Transplantation
High Risk MDS
MDS
AML
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2011-10-13
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of panobinostat
timeFrame: after 28 days of administration
measure: Dose-limiting toxicity (MTD) of Panobinostat
timeFrame: after 28 days of administration
Secondary outcomes:
measure: Cumulative incidence of hematologic relapse and death
timeFrame: one year after HSCT
measure: Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy
timeFrame: patients will be followed for up to 2 years depending on the duration of study participation
measure: Time to complete donor chimerism
timeFrame: patients will be followed for up to 2 years depending on the duration of study participation
measure: Cumulative incidence of extensive chronic GvHD
timeFrame: one year after HSCT
measure: Duration of complete donor chimerism
timeFrame: patients will be followed for up to 2 years depending on the duration of study participation
measure: Cumulative incidence of severe acute GvHD
timeFrame: one year after HSCT
measure: patient-reported health-related quality of life
timeFrame: after 3 months of administration and one month after last intake of study drug
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Essen
country: Germany
facility: University Hospital Essen
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Marburg
country: Germany
facility: University Hospital Marburg
Study officials:
affiliation: Johann Wolfgang Goethe University Hospital
name: Gesine Bug, MD
role: PRINCIPAL_INVESTIGATOR
References: