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)

March 19, 2018 updated by: Gesine Bug, Johann Wolfgang Goethe University Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Düsseldorf, Germany, 40225
        • University Hospital Düsseldorf
      • Essen, Germany, 45147
        • University Hospital Essen
      • Frankfurt am Main, Germany, 60590
        • University Hospital Frankfurt
      • Hamburg, Germany, 20246
        • University Hospital Hamburg-Eppendorf
      • Mainz, Germany, 55131
        • University Hospital Mainz
      • Marburg, Germany, 35043
        • University Hospital Marburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • LBH589
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 Names:
  • LBH589
Experimental: Panobinostat Arm B
Drug: Panobinostat
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
Other Names:
  • LBH589
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 Names:
  • LBH589

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum tolerated dose (MTD) of panobinostat
Time Frame: after 28 days of administration
after 28 days of administration
Dose-limiting toxicity (MTD) of Panobinostat
Time Frame: after 28 days of administration
after 28 days of administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Cumulative incidence of hematologic relapse and death
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: one year after HSCT
one year after HSCT
Duration of complete donor chimerism
Time Frame: 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
Time Frame: one year after HSCT
one year after HSCT
patient-reported health-related quality of life
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johann Wolfgang Goethe University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gesine Bug, MD, Johann Wolfgang Goethe University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 13, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 20, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLBH589 BDE05T

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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