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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Information provided by (Responsible Party):
Gesine Bug, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01451268
First received: September 30, 2011
Last updated: April 15, 2014
Last verified: September 2013
  Purpose

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 18 months after HSCT
  • To evaluate immunoregulatory properties of panobinostat 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 Intervention Phase
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Drug: Panobinostat
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of panobinostat [ Time Frame: after 28 days of administration ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity (MTD) of Panobinostat [ Time Frame: after 28 days of administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Cumulative incidence of hematologic relapse and death [ Time Frame: one year after HSCT ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to complete donor chimerism [ Time Frame: patients will be followed for up to 2 years depending on the duration of study participation ] [ Designated as safety issue: No ]
  • Cumulative incidence of extensive chronic GvHD [ Time Frame: one year after HSCT ] [ Designated as safety issue: No ]
  • Duration of complete donor chimerism [ Time Frame: patients will be followed for up to 2 years depending on the duration of study participation ] [ Designated as safety issue: No ]
  • Cumulative incidence of severe acute GvHD [ Time Frame: one year after HSCT ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: January 2011
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451268

Locations
Germany
University Hospital Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Contact: Guido Kobbe, MD       kobbe@med.uni-duesseldorf.de   
University Hospital Essen Recruiting
Essen, Germany, 45147
Contact: Michael Koldehoff, Priv.-Doz. MD       michael.koldehoff@uk-essen.de   
University Hospital Frankfurt Recruiting
Frankfurt am Main, Germany, 60590
Contact: Gesine Bug, MD       g.bug@em.uni-frankfurt.de   
University Hospital Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Nicolaus Kroeger, Prof       nkroeger@uke.uni-hamburg.de   
University Hospital Mainz Recruiting
Mainz, Germany, 55131
Contact: Eva Wagner, MD       eva.wagner@unimedizin-mainz.de   
University Hospital Marburg Recruiting
Marburg, Germany, 35043
Contact: Andreas Neubauer, Prof.       neubauer@mailer.uni-marburg.de   
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Investigators
Principal Investigator: Gesine Bug, MD Johann Wolfgang Goethe University Hospitals
  More Information

Additional Information:
No publications provided

Responsible Party: Gesine Bug, Senior physician hematology, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01451268     History of Changes
Other Study ID Numbers: CLBH589 BDE05T
Study First Received: September 30, 2011
Last Updated: April 15, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on July 22, 2014