Overview

This trial is active, not recruiting.

Conditions myelodysplastic syndrome, acute myeloid leukemia
Treatments panobinostat
Phase phase 1/phase 2
Target HDAC
Sponsor Johann Wolfgang Goethe University Hospital
Start date January 2011
End date July 2017
Trial size 62 participants
Trial identifier NCT01451268, CLBH589 BDE05T

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
panobinostat LBH589
10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year
(Experimental)
panobinostat 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

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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)
Principal investigator Gesine Bug, MD
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Johann Wolfgang Goethe University Hospital.