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.
Verified September 2012 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Johann Wolfgang Goethe University Hospitals
Information provided by (Responsible Party):
Gesine Bug, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01451268
First received: September 30, 2011
Last updated: September 3, 2012
Last verified: September 2012
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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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01451268
Locations
| Germany | |
| University Hospital Düsseldorf | Recruiting |
| Düsseldorf, Germany, 40225 | |
| Contact: Guido Kobbe, MD 00492118118524 kobbe@med.uni-duesseldorf.de | |
| Johann Wolfgang Goethe University Hospitals | Recruiting |
| Frankfurt am Main, Germany, 60590 | |
| Contact: Gesine Bug, MD 00496963014802 g.bug@em.uni-frankfurt.de | |
| University Hospital Hamburg-Eppendorf | Recruiting |
| Hamburg, Germany, 20246 | |
| Contact: Nicolaus Kroeger, Prof 0049407410 ext 54850 nkroeger@uke.de | |
| University Hospital Marburg | Recruiting |
| Marburg, Germany, 35043 | |
| Contact: Andreas Neubauer, Prof. 004964215866272 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: | September 3, 2012 |
| 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 May 16, 2013