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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)

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ClinicalTrials.gov Identifier: NCT01451268
Recruitment Status : Active, not recruiting
First Posted : October 13, 2011
Last Update Posted : September 2, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Acute Myeloid Leukemia Drug: Panobinostat Phase 1 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2011
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : August 2017


Arms and Interventions

Arm Intervention/treatment
Experimental: Panobinostat Arm A Drug: Panobinostat
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Other Name: LBH589
Experimental: Panobinostat Arm B Drug: Panobinostat
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
Other Name: LBH589


Outcome Measures

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of panobinostat [ Time Frame: after 28 days of administration ]
  2. Dose-limiting toxicity (MTD) of Panobinostat [ Time Frame: after 28 days of administration ]

Secondary Outcome Measures :
  1. Cumulative incidence of hematologic relapse and death [ Time Frame: one year after HSCT ]
  2. Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy [ Time Frame: patients will be followed for up to 2 years depending on the duration of study participation ]
  3. Time to complete donor chimerism [ Time Frame: patients will be followed for up to 2 years depending on the duration of study participation ]
  4. Cumulative incidence of extensive chronic GvHD [ Time Frame: one year after HSCT ]
  5. Duration of complete donor chimerism [ Time Frame: patients will be followed for up to 2 years depending on the duration of study participation ]
  6. Cumulative incidence of severe acute GvHD [ Time Frame: one year after HSCT ]
  7. patient-reported health-related quality of life [ Time Frame: after 3 months of administration and one month after last intake of study drug ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01451268


Locations
Germany
University Hospital Düsseldorf
Düsseldorf, Germany, 40225
University Hospital Essen
Essen, Germany, 45147
University Hospital Frankfurt
Frankfurt am Main, Germany, 60590
University Hospital Hamburg-Eppendorf
Hamburg, Germany, 20246
University Hospital Mainz
Mainz, Germany, 55131
University Hospital Marburg
Marburg, Germany, 35043
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
Investigators
Principal Investigator: Gesine Bug, MD Johann Wolfgang Goethe University Hospital
More Information

Additional Information:
Responsible Party: Gesine Bug, Senior physician hematology, Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier: NCT01451268     History of Changes
Other Study ID Numbers: CLBH589 BDE05T
First Posted: October 13, 2011    Key Record Dates
Last Update Posted: September 2, 2016
Last Verified: September 2016

Keywords provided by Gesine Bug, Johann Wolfgang Goethe University Hospital:
60 to 150 Days After Allogeneic Stem Cell Transplantation
High Risk MDS
MDS
AML

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action