Myelodysplastic SyndromePhase 1/2PANOBESTNCT01451268
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)
A Phase 1/2 study testing Panobinostat in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Johann Wolfgang Goethe University Hospital at 6 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- Panobinostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 6 sitesGermany
- Study dates
- Jan 2011to Apr 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
University Hospital Düsseldorf
Düsseldorf, 40225
University Hospital Essen
Essen, 45147
University Hospital Frankfurt
Frankfurt am Main, 60590
University Hospital Hamburg-Eppendorf
Hamburg, 20246
University Hospital Mainz
Mainz, 55131
University Hospital Marburg
Marburg, 35043
About this study
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)
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
Read more
- 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.
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Being tested
- Panobinostat
- Keywords
- 60 to 150 Days After Allogeneic Stem Cell Transplantation, High Risk MDS, MDS, AML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
PanobinostatDrug
Also called LBH589
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
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat Arm A | Experimental | Not described Receives: Drug: Panobinostat |
| Panobinostat Arm B | Experimental | Not described Receives: Drug: Panobinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of panobinostat
Measured: after 28 days of administration
Dose-limiting toxicity (MTD) of Panobinostat
Measured: after 28 days of administration
Secondary outcomes (7)
Cumulative incidence of hematologic relapse and death
Measured: 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
Measured: patients will be followed for up to 2 years depending on the duration of study participation
Time to complete donor chimerism
Measured: patients will be followed for up to 2 years depending on the duration of study participation
Cumulative incidence of extensive chronic GvHD
Measured: one year after HSCT
Duration of complete donor chimerism
Measured: patients will be followed for up to 2 years depending on the duration of study participation
Cumulative incidence of severe acute GvHD
Measured: one year after HSCT
patient-reported health-related quality of life
Measured: after 3 months of administration and one month after last intake of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2011 (estimated)
- Study startJan 2011
- Primary completionApr 2018 (estimated)
- Study completionApr 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johann Wolfgang Goethe University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gesine Bug, Johann Wolfgang Goethe University Hospital
- Investigators
- Gesine Bug, MD, Principal investigator, Johann Wolfgang Goethe University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451268
- Sponsor's protocol ID
- CLBH589 BDE05T
- Acronym
- PANOBEST
- Status last verified
- Mar 2018
- First submitted
- 30 Sep 2011
- Last updated
- 20 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01451268
- Acronym / sponsor ID
- PANOBEST / CLBH589 BDE05T
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Keywords
- 60 to 150 Days After Allogeneic Stem Cell Transplantation, High Risk MDS, MDS, AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Johann Wolfgang Goethe University HospitalUniversity, hospital or other
- Study start
- Jan 2011 (actual)
- Primary completion
- Apr 2018 (estimated)
- Study completion
- Apr 2018 (estimated)
- First posted
- 13 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panobinostat Arm A | Experimental | Drug: Panobinostat |
| Panobinostat Arm B | Experimental | Drug: Panobinostat |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- AML (except acute promyelocytic leukemia, AML M3) with high-risk features defined as one or more of the following criteria:
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanobinostatAlso: LBH58910mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year | Drug | Panobinostat Arm A |
| PanobinostatAlso: LBH589Start 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 | Drug | Panobinostat Arm B |
Primary outcome
Maximum tolerated dose (MTD) of panobinostat
Time frame: after 28 days of administration
Dose-limiting toxicity (MTD) of Panobinostat
Time frame: after 28 days of administration
7 secondary outcomes
Cumulative incidence of hematologic relapse and death
Time frame: 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
Time to complete donor chimerism
Time frame: 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
Duration of complete donor chimerism
Time frame: 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
patient-reported health-related quality of life
Time frame: after 3 months of administration and one month after last intake of study drug
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gesine Bug, MD principal investigator
Johann Wolfgang Goethe University Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Johann Wolfgang Goethe University Hospital at 6 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of panobinostat (time frame: after 28 days of administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2018.