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)

NCT ID: NCT01451268

Last Updated: 2018-03-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2018-04-30

Brief 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.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panobinostat Arm A

Group Type: EXPERIMENTAL

Panobinostat

Intervention Type: DRUG

10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year

Panobinostat Arm B

Group Type: EXPERIMENTAL

Panobinostat

Intervention Type: DRUG

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

Interventions

Panobinostat

10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

LBH589; LBH589

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johann Wolfgang Goethe University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gesine Bug

Senior physician hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gesine Bug, MD

Role: PRINCIPAL_INVESTIGATOR

Johann Wolfgang Goethe University Hospital

Locations

University Hospital Düsseldorf

Düsseldorf, , Germany

University Hospital Essen

Essen, , Germany

University Hospital Frankfurt

Frankfurt am Main, , Germany

University Hospital Hamburg-Eppendorf

Hamburg, , Germany

University Hospital Mainz

Mainz, , Germany

University Hospital Marburg

Marburg, , Germany

Countries

Germany

Related Links

http://www.studienregister-online.de

Trial register of the Kompetenznetz Leukämien, additional trial information

Other Identifiers

CLBH589 BDE05T

Identifier Type: -

Identifier Source: org_study_id