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Study with panobinostat maintenance therapy following stem cell transplantation in patients with high risk Myelodysplastic Syndrome or Acute Myeloic Leukemia

Phase 1
Conditions
MDS and AML in patients with high risk features after hemapoietic stem cell transplantation with reduced conditioning
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2010-018699-26-DE
Lead Sponsor
Goethe Universität Frankfurt
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
62
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
•CMML with = 5% bone marrow blasts

and
•Allogeneic HSCT with reduced intensity conditioning performed within 60 - 150 days prior to study entry
•Complete hematologic remission documented by bone marrow aspiration within 28 days prior to study entry

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

•Active acute GvHD overall grade 2 - 4
•Prior treatment with a DAC inhibitor
• Concomittant antileukemic medication
•Patients with impaired cardiac function or other concurrent severe and/or uncontrolled medical conditions
•Clinical symptoms suggesting CNS leukemia
•Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after HSCT and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk MDS or AML;Secondary Objective: •To determine safety and tolerability of panobinostat<br>•To determine overall and disease-free survival at 12 months after HSCT<br>•To evaluate immunoregulatory properties of panobinostat<br>•To evaluate patient-reported health-related quality of life (HRQL)<br><br>;Primary end point(s): Maximum tolerated dose (MTD) and dose-limiting toxicity (MTD) of panobinostat ;Timepoint(s) of evaluation of this end point: after 28 days of administration
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): •Safety and tolerability as determined by type, frequency, severity and relationship of adverse events to study treatment<br>•Cumulative incidence of hematologic relapse and death at one year after HSCT<br>•Cumulative incidence of severe acute GvHD and extensive chronic GvHD at one year after HSCT<br>•Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy <br>•Time to and duration of complete donor chimerism<br>•HRQL at baseline, day 85, and 28 days after last intakte of study drug<br><br>;Timepoint(s) of evaluation of this end point: if not other specified above: after one year of administration and one additional year of follow-up
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